TREATMENT OF BLADDER PAIN SYNDROME FIELD OF THE INVENTION The present invention relates to the treatment of bladder pain syndrome (BPS), in particular to the treatment of Interstitial Cystitis (IC). BACKGROUND BPS is a chronic bladder health issue affecting around 6-14M patients in the US (ie.5-11% of the adult US population). The International Continence Society (ICS) defines BPS as a condition characterised by chronic (>6 months) pelvic pain, pressure or discomfort perceived to be related to the urinary bladder, and that is accompanied by at least one other urinary symptom such as persistent urge to void or frequency. Frequency is the need to pass urine more often than normal. The average person urinates no more than 7 times per day and does not have to get up at night more than once to use the bathroom. A BPS sufferer has to urinate frequently day and night, and as frequency becomes more severe, this leads to urgency. For some patients, this urge to urinate never goes away, even immediately after voiding. IC is a more severe or advanced form of BPS, and is further characterised by the presence of “typical cytoscopic and histological features”. For example, when compared with BPS (non-IC) patients, IC patients have a higher incidence and degree of denuded epithelium, ulceration, pyuria and/ or submucosal inflammation. IC might be better described as a chronic submucosal inflammatory disease. Whilst the specific cause of BPS is unknown, the following are believed to be contributing factors: - a defect in the bladder tissue that allows potential irritants present in urine to penetrate the bladder wall; - mast cell hyperfunction and excess secretion of inflammatory signals (eg. histamine); - a contaminant presence in urine that damages the bladder wall; - hypersensitivity of local afferent nerves such that pain is caused by events that are not normally painful (eg. bladder filling); and - autoimmunity.   Urine is formed by the nephrons of the kidney and is transported to the urinary bladder for storage before being expelled via the urethra. This process of cyclical filling-and-emptying is known as micturition. As the bladder fills, it stretches, simulating afferent signals. Conversely, efferent signals result in contraction of the bladder musculature and relaxation of the urethral sphincter, respectively. In addition to mechanoreceptors, various psychological factors (eg. stress, sense of acceptable surroundings, and emotional status) play a crucial role in the timing and setting of micturition. Self-evidently, the urinary bladder has excellent elastic properties. These properties flow from the bladder wall structure, which organizes into the following layers (from inside-to-outside): - Epithelial lining; - Lamina propria; - Muscularis propria; and - Serosa/ adventitia. The epithelial cells of the bladder lining provide a critical barrier that prevents irritants present in urine from crossing the bladder lining and contacting the underlying cells and connective tissues that surround the bladder lumen. Indeed, the epithelial cells of the bladder form a highly specialized stratified epithelium, the urothelium, designed for this specific purpose. In more detail, the urothelium is composed of three layers: - the apical layer, which is the innermost layer and serves as the principal barrier between the bladder lumen and the underlying tissue. This highly specialised layer is formed of a single layer of cells (“umbrella cells”) that cooperate via tight intercellular junctions to form an impermeable barrier. Another important role performed by the umbrella cells is that they accommodate bladder stretch. This is achieved by the release of uroplakin (via uroplakin-containing fusiform vesicles), which forms a superficial plaque layer that covers the umbrella cells. And, as the bladder wall relaxes, this reservoir of uroplakin is returned to the umbrella cells by SNARE-mediated endocytosis; - the intermediate layer, which is formed from two to three layers of polygonal cells; and - the basal layer, which is formed from two to three layers of small cuboidal cells. In a relaxed (ie. not distended) urinary bladder, the urothelium is five to seven layers thick. When in this not distended conformation, the typical capacity of a (human) bladder in a healthy individual is about 500 ml, When the urinary bladder fills with urine, the bladder wall stretches to accommodate the increased volume and, when in this distended form, the urothelium reorganizes into two or three layers without any structural damage.   The lamina propria forms an extracellular matrix that separates the urothelium from the underlying muscularis propria (detrusor muscle). Said matrix comprises many specialised cell types (eg. elastic fibers, capillaries, afferent nerve endings, interstitial cells of Cajal, an indistinct smooth muscle layer, and the muscularis mucosae), and acts as the “functional centre” of the bladder. In this regard, the lamina propria regulates the afferent limb of the micturition reflex, and the interstitial cells of Cajal are believed to act as nerve signal transducers to the bladder's smooth muscle cells. Thus, the lamina propria serves as a capacitance layer of the bladder. The muscularis propria is also known as the detrusor muscle. It is innervated by efferent (motor) nerves and consists of three layers: inner longitudinal, middle circular, and outer longitudinal. The serosa and adventitia are thin connective tissue layers that form the outermost layers of the bladder. These layers are collectively responsible for maintaining homeostatic control of the bladder (eg. micturition), whilst the bladder wall lining insulates and protects adjacent tissues and organs from contact by urine stored in the bladder (incl. toxic solutes and metabolites present in the urine). In doing so, the bladder wall lining provides a highly efficient barrier that is impermeable to urine. However, an adverse consequence of this highly specialised function is that the bladder wall is also impermeable to potential therapeutic molecules. This poses a significant challenge for any therapeutic treatment of BPS and/ or IC as the therapeutic molecule must first cross the bladder wall barrier before it can deliver a clinically relevant effect on the target cells of interest, which are located in the deeper underlying layers of the bladder wall, Whilst -non-invasive approaches have attracted some interest, a common problem with these methods is that they offer, at best, limited beneficial effect that is very slow acting (requiring up to 6 months). Frequent, repeated administration is also required. To-date, Elmiron ^R (ie. pentosane polysulfate sodium) remains the sole drug approved by the FDA for the treatment of BPS/ IC by oral administration. Pentosane polysulfate is similar in structure to the natural glycosaminoglycan coating of the inner lining of the bladder and is believed to provide transient repair the said lining. Whilst it’s precise mechanism of action is unknown it is understood that Elmiron ^R adheres to and forms a layer on the luminal side of the bladder wall. Elmiron ^R   therefore acts as a type of chemical filler or sealant and effectively papers-over any damaged areas of the urothelium. Invasive approaches address these shortfalls and are the preferred method of intervention for treating BPS and/ or IC. This is despite the fact that invasive methods routinely involve some aspect of physical intervention, which gives rise to additional patient management considerations ranging from anaesthesia to intravenous sedation. Of the most common physical intervention procedures is intradetrusor injection (see Fig. 1), which involves the careful manipulation of a device through the opening and along the length of the urethra, and into the bladder of a patient. Cytoscopic guidance then allows sequential manoeuvring of a needle to multiple, predetermined intramuscular injection sites located across the bladder wall lining. Each injection involves penetration of the needle through the bladder wall lining (into the detrusor muscle) and results in the delivery of a metred dose of therapeutic agent at each injection site. Adverse consequences of this procedure include local bleeding and pain, and can give rise to significant patient management issues. In particular, the side effects of this procedure, such as the local bleeding and pain can lead to overall poor patient satisfaction, which in turn may result in reduced patient compliance with this treatment regimen. Another approach is that of intravesical instillation (see Fig.2), which involves insertion of a catheter into a patient’s urethra and drainage of any urine present in the bladder. A small volume (eg. 50 ml) of medication is then slowly instilled through the catheter and into the bladder. The catheter is removed and the patient instructed to resume normal daily activities though not to empty their bladder for at least 15 minutes, preferably at least 90 minutes. In doing so, the medication is allowed to contact and potentially treat the whole bladder wall lining. Unfortunately, however, this procedure fails to address the impermeable barrier problem posed by the bladder wall lining and thus has limited in that it is only suited for therapeutics that act on the luminal side of the bladder wall lining. Attempts have been made to modify this procedure to extend the therapeutic options available to include the targeting of cells located in the deeper layers of the bladder wall. One such approach has been to rely on use of chemical denuding agents (eg. dimethyl sulphoxide (DMSO), protamine sulphate, hyaluronan-phosphatidylethanolamine), which are dissolved in the liquid instillation mix and administered to a patient as part of the standard instillation protocol. For example, DMSO may be administered as a single-agent instillation at a 50% concentration or, more commonly, as part of a ‘cocktail’ with methylprednisolone or hydrocortisone, alkalized lidocaine and heparin sulfate. Once administered, the denuding   agents attack any cells they come into contact with, progressively stripping-away cells from the urothelial layer and permeabilising the bladder wall. Unfortunately, instillation with denuding agents has not proven to be well suited as a method of choice for treating BPS and/ or IC. There are several reasons for this, not least that the chemical denuding agents are toxic (typically non-discriminatory) irritants and thus any extended exposure, for example to a patient or physician, should be avoided. Therefore, instillation with denuding agents is unsuitable for repeated uses. Furthermore, once initiated, it is difficult to maintain adequate control of the denuding process, which in turn makes the process unpredictable and thus unreliable. Contributing factors include chemical agent variables (eg. the choice and concentration of agent), instillation variables (eg. the period of exposure to agent), and patient-specific variables (eg. the extent of existing bladder wall damage, and responsiveness to the selected therapeutic molecule or regimen). The bladder wall lining (urothelium) is not the only structural challenge one must address when considering delivery of a therapeutic molecule to the relevant target cells for treatment of BPS and/ or IC. For example, when the target cells are located in the deeper layers of the bladder wall, the therapeutic molecule must be able to penetrate the underlying layers of the bladder wall in order to reach said target cells, where it can then deliver its therapeutic effect. Unsurprisingly then, the physical constraints imposed by the bladder wall structure therefore inherently favour small molecule therapeutics, making such molecules the preferred class of molecule and treating BPS and/ or IC. Therapeutic intervention is further vexed by a need to ensure the therapeutic molecule is selectively delivered to the relevant target cells, thereby avoiding or minimising any undesirable off-site target effects. In the context of treating BPS and/ or IC, this requires the selective targeting of sensory afferent over efferent nerve fibres present in the underlying tissues of the bladder wall. The use of clostridial neurotoxins, in particular, BoNT/A, for the treatment of BPS via intradetrusor injections is known. Intradetrusor injections of BoNT/A are highly invasive and simultaneously target all three levels of innervation of the bladder wall, namely: the urothelium; the afferent terminals of the lamina propria; and the efferent terminals of the detrusor muscle (see Figure 3). This procedure fails to achieve selective targeting of BoNT/A to the sensory afferent fibres (in preference to efferent fibres). Moreover, the binding of BoNT/A to efferent terminals of the detrusor muscle can result in unwanted side effects such as bleeding.   On the other hand, intraluminal instillation of BoNT/A (without injection) failed to deliver BoNT/A into the bladder wall due to impermeability of the bladder urothelium to large macromolecules and degradation of the BoNT/A by urine proteases – see Khera, M. et al. (2005) Urology, 66, 208-212; and Shimizu, S. (2012) J. Urol., 187, e370. Attempts have been made to address the degradation effect by use liposome-encapsulated BoNT/A. Whilst limited delivery of BoNT/A has been reported (when co-administered via intraluminal instillation with DMSO, protamine sulphate or hyaluronan-phosphatidylethanolamine), this denuding agent approach has failed to provide an approved method offering any significant improvement over intradetrusor injections with BoNT/A, which continues to be the current method of choice for therapeutic intervention of BPS. Limited delivery of BoNT/A has also been reported when administered (via intraluminal instillation) in the form of hydrogel formulations or liposome encapsulated formulations. However, similar to the denuding agent approaches, the use of hydrogels or liposomes has failed to provide an approved method offering any significant improvement over BoNT/A intradetrusor injections, which continues to be the current method of choice for therapeutic intervention of BPS. Accordingly, there is a need in the art for a method of treating BPS and/ or IC that selectively targets sensory afferent fibres in preference to efferent fibres present in the bladder wall, whilst being minimally invasive (eg. less invasive than intradetrusor injections). There is also a need to avoid the use of denuding agents. The present invention addresses one or more of the above-identified problems. SUMMARY OF THE INVENTION The present invention relates to the use of clostridial neurotoxins, such as botulinum neurotoxins (BoNTs), as a therapeutic for the treatment of bladder pain syndrome (BPS), particularly Interstitial cystitis (IC) in a subject in need thereof. In more detail, for the first time the present inventors have surprisingly found that administration of a clostridial neurotoxin (eg. BoNT/A) by a unique approach involving a light pressure filling of the bladder with a solution containing said neurotoxin can drastically improve a patient’s   quality of life by alleviating or eliminating pain associated with BPS, particularly IC, with little to no side effects, unlike conventional methods. A surprising finding by the inventors is that this approach generates a light mechanical force against the urothelial layer of the bladder that is sufficient to allow the clostridial neurotoxin to diffuse across the urothelial layer and into the lamina propria, whilst limiting further diffusion of the neurotoxin into deeper layers of the bladder wall, in particular into the detrusor muscle. Said light pressure driven diffusion of the clostridial neurotoxin allows the toxin to target the primary sensory afferent nerves located within the lamina propria, suppressing neurotransmitter release therefrom and alleviating the sensation of pain. This is possible because the urothelial layer of the bladder in subjects suffering from BPS, particularly IC, is damaged and porous, and thus the solution is able to pass through this layer with the assistance of said light pressure filling technique of the present invention. A further advantage is that no needles or abrasive excipients are needed and thus a simple saline-based solution is needed. This is in contrast to the existing methods wherein painful needle injections or harsh and irritating formulations are used to bring the clostridial neurotoxin (e.g. BoNT) in the lamina propria and beyond. Therefore, unlike conventional methods, which purposely damage the urothelial cell layer and beyond, the administration technique (light pressure filling) of the present invention has no effect or very little effect on the integrity of the urothelial cell layer, e.g. it does not cause further damage than is already present. In practice, a patient’s bladder is typically flushed/cleaned prior to light-pressure filling. Thereafter, clostridial neurotoxin solution is infused into the bladder, for example via simple catheter means, which causes light pressure to be applied to the urothelial layer. This infusion is allowed to proceed up to, though not beyond, the point at which the patient feels the urge to void his/her bladder. In a healthy adult, this (typically) occurs when the bladder is holding a volume of approximately 300-400 ml, though in a BPS patient, this can typically occur when the bladder is holding 200-300 ml, sometimes less. The urge to pass urine arises when stretch receptors present in the bladder signal the parasympathetic nervous system to stimulate the muscarinic receptors of the detrusor muscle to contract, thereby initiating micturition. Thus, a little trial and error may be required on a patient-by-patient basis to establish the relevant threshold volume of liquid that will trigger bladder emptying. One then simply works back from this threshold volume of liquid to calculate a reduced volume (e.g. by 5% or 10%) to build in a comfort factor to ensure the patient won’t void his/her bladder during treatment with clostridial   neurotoxin solution. Once the desired volume of clostridial neurotoxin has been infused, the catheter is closed, and the solution allowed to diffuse across the urothelial layer. Importantly, the inventors have observed that said light-pressure driven diffusion of clostridial neurotoxin is typically limited to diffusion within the lamina propria. In particular, said diffusion does not extend to the bladder muscle layer, such that the clostridial neurotoxin does not target the efferent terminals of the detrusor muscle, unlike conventional intradetrusor injections and therefore, avoids unwanted side effects such as bleeding and muscle paralysis. Instead, the new method allows for the accurate delivery of a clostridial neurotoxin, where said neurotoxin disperses systemically throughout the urothelial layer and lamina propria layer of the bladder wall, to target the afferent nerve terminals (sensory terminals capable of signalling pain) localised within the lamina propria layer (see Figure 4). The new administration method of the present invention (light pressure filling) is advantageous in that it allows for a simplified, painless and non-invasive mode of administration (needle-free dosing of clostridial neurotoxins) and thus the procedure can be performed not only by nurses but also potentially by patients themselves. The non-invasive nature of this approach combined with the desired therapeutic outcome leads to improved overall patient satisfaction, which in turn enhances patient compliance with this treatment regimen. DETAILED DESCRIPTION In one aspect, the invention provides a method of treating a patient suffering from bladder pain syndrome, said method comprising: administering a solution containing a clostridial neurotoxin into the bladder of the patient; increasing the volume of solution comprising the clostridial neurotoxin present within the bladder, thereby applying a mechanical force against the inner surface of the urothelial layer; and maintaining said volume of solution comprising the clostridial neurotoxin present within the bladder at a volume that does not give rise to patient micturition and for a duration of at least 30 minutes, thereby allowing the clostridial neurotoxin to diffuse across the urothelial layer and into the lamina propria, where the clostridial neurotoxin binds to primary sensory afferent nerve fibres, suppresses secretion of neurotransmitters therefrom, and alleviates bladder pain. In one aspect the invention provides a solution comprising a clostridial neurotoxin for use in a method of treating a patient suffering from BPS, said method comprising:   administering the solution containing the clostridial neurotoxin into the bladder of the patient; increasing the volume of solution comprising the clostridial neurotoxin present within the bladder, thereby applying a mechanical force against the inner surface of the urothelial layer; and maintaining said volume of solution comprising the clostridial neurotoxin present within the bladder at a volume that does not give rise to patient micturition and for a duration of at least 30 minutes, thereby allowing the clostridial neurotoxin to diffuse across the urothelial layer and into the lamina propria, where the clostridial neurotoxin binds to primary sensory afferent nerve fibres, suppresses secretion of neurotransmitters therefrom, and alleviates bladder pain. The bladder wall comprises three cellular layers; the urothelium, lamina propria and detrusor muscle. The urothelium, the innermost layer of the bladder wall, is a unique, highly specialised epithelial lining and acts as a barrier separating the contents of the bladder lumen from the tissues underlying the urothelium. The lamina propria is a loose layer of connective tissue which separates the urothelium from the detrusor muscle of which is composed of smooth muscle fibers that are longitudinal and circular. Advantageously, the inventors observed that by filling the bladder of a patient suffering from BPS/IC with a solution comprising a clostridial neurotoxin up to, though not beyond, the point at which the patient feels the urge to void his/her bladder, this causes a light pressure to be applied to the urothelial layer, allowing the light-pressure driven diffusion of clostridial neurotoxin across said layer and into the lamina propria. Various methods can be used to ascertain a patient’s threshold volume of liquid that will trigger bladder emptying. For example, a voiding diary, uroflowmetry, ultrasound scanning and cystometry may be used. A voiding diary may be a record of timings of a patient’s daily fluid intake and micturates (including incidental leakages) over a period of 24 hours. Uroflowmetry may involve allowing a patient to micturate, and where a uroflowmeter records the total volume, speed and length of time at which urine is passed from the bladder. A bladder scan may be subsequently performed to assess whether there is residual volume in the   patient’s bladder. A threshold volume of liquid that triggers bladder emptying may then be calculated based on findings from the uroflowmeter and the bladder scan. Ultrasound scanning may involve scanning the pelvic area of a patient who has a full bladder (before micturition), to determine the amount of fluid in the patient’s bladder. An ultrasound scan may provide information on a patient’s bladder size, fullness and/or the lining of the bladder. Cystometry may be performed by placing a 5-F catheter into the patient’s bladder (whilst the patient is in a sitting position) and infusing saline into the bladder at a rate of 50 ml per minute. The threshold volume of liquid that will trigger bladder emptying may be determined by noting the amount of saline (in ml) infused into the patient’s bladder until the patient cannot prolong micturition. The skilled person will appreciate that the threshold volume of liquid that triggers micturition may differ on a patient-by-patient basis, where the patient has BPS/IC. Moreover, the skilled person will appreciate that differences in said threshold volume may differ between a BPS/IC patient and a healthy patient. To prevent micturition during treatment, whilst simultaneously allowing for light pressure to be applied to the urothelial layer, a reduced volume of solution comprising a clostridial neurotoxin (e.g. below the threshold volume of liquid that triggers micturition) may be administered. A volume of solution comprising a clostridial neurotoxin for administration to a patient may be reduced by at least 5%, 10%, 15%, 20%, 25%, 30% when compared to the threshold volume of liquid that triggers micturition in the same patient. A volume of solution comprising a clostridial neurotoxin for administration to a patient may be reduced by less than or equal to 70%, 60%, 50% or 40% when compared to the threshold volume of liquid that triggers micturition in the same patient. A volume of solution comprising a clostridial neurotoxin for administration to a patient may be reduced by 5-70%, 10-60%, 15-50%, 20-40% or 25-30% when compared to the threshold volume of liquid that triggers micturition in the same patient. A reduced volume of solution comprising a clostridial neurotoxin for administration to a patient may be at least 150, 175, 200, 225, 250, 275 or 300 ml. A reduced volume of solution comprising a clostridial neurotoxin for administration to a patient may be less than or equal to 400, 375, 350, 325, 300, 275 or 250 ml. A reduced volume of solution comprising a clostridial   neurotoxin for administration to a patient may be 150-400, 175-375, 200-350, 225-325 or 250- 300 ml. In one embodiment a single treatment infusion with a solution comprising a clostridial neurotoxin is effected for a defined duration, for example, for a duration of at least 15 minutes, 20 minutes, 25 minutes, 30 minutes or 40 minutes, preferably for at least 45 minutes, more preferably for at least 50 minutes (e.g. for at least 1 hour). In one embodiment, a single treatment infusion with a solution comprising a clostridial neurotoxin is effected for a duration of less than or equal to 2 hours, 1 hour and 45 minutes, 1 hour and 30 minutes, or 1 hour and 25 minutes, preferably for less than or equal to 1 hour and 15 minutes, more preferably for less than or equal to 1 hour and 10 minutes (e.g. for at least 1 hour). In one embodiment, a single treatment infusion with a solution comprising a clostridial neurotoxin is effected for a duration of 15 minutes to 2 hours, 30 minutes to 1 hour and 45 minutes, 45 minutes to 1 hour and 30 minutes, preferably 45 minutes to 1 hour and 15 minutes, more preferably 50 minutes to 1 hour and 10 minutes (e.g. for 1 hour). Following this, the patient may then be asked by a practitioner to micturate to remove the solution from said patient’s bladder. The patient may receive a course of treatment which includes multiple treatment infusions over a defined period of time, such as multiple treatment infusions over a 2- week period. In one embodiment, a solution comprising a clostridial neurotoxin is administered by light pressure filling as part of a course of treatment, in which the course of treatment includes multiple, discrete infusions over a defined period of time of at least 2 weeks, 3 weeks, 4 weeks, preferably at least 5 weeks, more preferably at least 6 weeks (e.g. at least 7 weeks). In one embodiment, a solution comprising a clostridial neurotoxin is administered by light pressure filling as part of a course of treatment, in which the course of treatment includes multiple, discrete infusions over a defined period of time of less than or equal to 12 weeks, 11 weeks or 10 weeks, preferably at less than or equal to 9 weeks, more preferably at less than or equal to 8 weeks (e.g. less than or equal to 7 weeks). In one embodiment, a solution comprising a clostridial neurotoxin is administered by light pressure filling as part of a course of treatment, in which the course of treatment includes multiple, discrete infusions over a defined period of time of 2-12 weeks, 3-11 weeks or 4-10 weeks, preferably 5-9 weeks, more preferably 6-8 weeks (e.g.7 weeks). Multiple, discrete infusions may be administered at a frequency of at least 1x or 2x per week. Multiple discrete infusions may be administered at a frequency of less than or equal to 4x, 3x   2x or 1x per week. Multiple discrete infusions may be administered at a frequency of 1-4x, 1- 3x or 2-3x per week, preferably 2-3x per week. The term “hydrodistension” may refer to a method in which the bladder is filled with a sterile liquid using a cystoscope until the bladder is overdistended. Hydrodistension may involve filling the bladder with a solution at a pressure of 60-80 cmH ₂ 0 (Inoue et al., “Hydrodistention of the bladder in patients with interstitial cystitis--clinical efficacy and its association with immunohistochemical findings for bladder tissues.” Hinyokika Kiyo 52(10) (2006):765-8). Hydrodistension relies on the use of a high pressure to over distend the bladder. The administration method of the present invention is different and not equal to hydrodistension. Thus, in one embodiment, the administration of a solution comprising a clostridial neurotoxin to a patient does not involve hydrodistension of the patient bladder. In one embodiment, the administration of a solution comprising a clostridial neurotoxin to a patient does not involve distending the bladder to at least a pressure of 50, 60, 70 or 80 cmH ₂ 0. In one embodiment, the administration of a solution comprising a clostridial neurotoxin to a patient does not involve distending the bladder to a pressure of less than or equal to 50-100, 60-90 or 70-80 cmH ₂ 0. In one embodiment, the clostridial neurotoxin selectively binds to primary sensory afferent nerve fibres. In one embodiment, the clostridial neurotoxin remains substantially within the lamina propria (preferably wherein the clostridial neurotoxin does not diffuse into the detrusor muscle of the bladder wall). Thus, advantageously, the method of the invention avoids targeting of the efferent nerve terminals localised in the detrusor muscle (which can cause bleeding and muscle paralysis), unlike conventional methods. In one embodiment the solution comprising clostridial neurotoxin disperses systemically throughout the lamina propria layer of the bladder wall and wherein the clostridial neurotoxin suppresses neurotransmitter release from substantially all parasympathetic afferent neurons present therein. Thus, the method of the invention may allow for the localised administration of a clostridial neurotoxin, unlike conventional methods (such as intradetrusor injections), with little or no spread to surrounding areas and with little systemic circulation (better targeting of the sensory fibers).   The term “systemically” may refer to the distribution of a solution throughout the whole of a tissue (preferably the lamina propria layer of the bladder wall). The solution may disperse uniformly in up to two layers of the bladder wall. The solution may disperse throughout the urothelial layer and/or the lamina propria. The solution may disperse systemically throughout the lamina propria layer, without dispersing into deeper layers of the bladder wall, such as the detrusor muscle. The term “substantially” in the context of suppressing neurotransmitter release from parasympathetic afferent neurons may mean suppressing neurotransmitter release from 50- 100%, 60-90% or 70-80% of parasympathetic afferent neurons present in the lamina propria layer. Preferably, the clostridial neurotoxin may suppress neurotransmitter release from 100% of parasympathetic afferent neurons present in the lamina propria layer. In one embodiment the solution is administered into the bladder via a catheter. In one embodiment the method is substantially non-invasive, preferably wherein said method imparts substantially no physical damage to the urothelial layer and/or lamina propria layer. Therefore, the present invention is advantageous in that it administers a clostridial neurotoxin through a non-invasive method that precludes the use of needles and is therefore painless. In one embodiment the solution may avoid further damage to the urothelial cells and lamina propria cells. In one embodiment the solution comprises (preferably consists) of a clostridial neurotoxin and a physiologically inert buffer. Preferably the physiologically inert buffer may be phosphate buffer saline. In one embodiment the approach of the present invention prevents further damage to the bladder wall as it avoids the use of a denuding agent. A denuding agent may be DMSO, protamine sulphate and/or hyaluronan-phosphatidylethanolamine. In other words, unlike conventional methods which administer chemical irritants such as DMSO to permeabilise the cells of the bladder wall, the present invention may administer a solution that is harmless (devoid of abrasive excipients such as DMSO) and which comprises the clostridial neurotoxin. The term “inert” may refer to a solution that may be chemically inactive, e.g. does not cause irritations or tissue damage. In one embodiment, the method may not give rise to patient micturition (preferably wherein the clostridial neurotoxin does not bind to parasympathetic efferent neurons to stimulate muscarinic receptors in the detrusor to contract the detrusor muscle). Thus, advantageously,   the method allows for sufficient time for the solution comprising the clostridial neurotoxin to diffuse across the urothelial layer, and, for the patient to benefit from the therapeutic effects of said solution, before the patient voids their bladder. In one embodiment, a single treatment infusion with a solution comprising a clostridial neurotoxin is administered for at least 1 hour. Taken together, the invention advantageously treats bladder pain syndrome by reducing or abolishing the level of pain perceived and improving a patient’s quality of life. Thus, in one embodiment bladder pain is reduced following treatment with a solution comprising a clostridial neurotoxin using the administration method of the present invention. For example, the level of pain in a BPS/IC patient may be reduced or abolished following treatment with a solution comprising a clostridial neurotoxin using the administration method of the present invention compared with a level of pain in a (control) patient that was not treated with the solution comprising the clostridial neurotoxin. In one embodiment bladder pain is reduced for at least 2 days following light pressure filling of the bladder with a solution comprising the clostridial neurotoxin. In one embodiment, bladder pain is reduced for at least 1 day, preferably at least 2 days, more preferably for at least 3 days (e.g. for at least 4 days) following light pressure filling of the bladder with a solution comprising the clostridial neurotoxin. In one embodiment, bladder pain is reduced for less than or equal to 9 days, 8 days or 7 days preferably for less than or equal to 6 days, more preferably for less than or equal to 5 days (e.g. for less than or equal to 4 days) following light pressure filling of the bladder with a solution comprising the clostridial neurotoxin. In one embodiment, bladder pain is reduced for 1-7 days or 2-6 days, preferably for 2-5 days, more preferably for 3-5 days (e.g. for 4 days) following light pressure filling of the bladder with a solution comprising the clostridial neurotoxin. In one embodiment, bladder pain is reduced for at least 3 months, 4 months, 5 months or 6 months, preferably for at least 7 months, more preferably for at least 8 months (e.g. for at least 9 months) following light pressure filling of the bladder with a solution comprising the clostridial neurotoxin. In one embodiment, bladder pain is reduced for less than or equal to 14 months, 13 months or 12 months, preferably for less than or equal to 11 months, more preferably for less than or equal to 10 months (e.g. for less than or equal to 9 months) following light pressure   filling of the bladder with a solution comprising the clostridial neurotoxin. In one embodiment, bladder pain is reduced at 6-14 months or 7-13 months, preferably at 8-12 months, more preferably at 9-11 months (e.g. for less than or equal to 9 months) following light pressure filling of the bladder with a solution comprising the clostridial neurotoxin. A type of pain which may represent bladder pain syndrome is allodynia. Allodynia means “other pain.” It is a pain that results from a stimulus that is not normally painful. A sufferer of ‘tactile’ allodynia (aka static tactile allodynia or mechanical allodynia) may experience pain when resting, such as pain, pressure and tenderness in the abdomen, or experience pain when micturating, Thus, allodynia is considered “pain due to a stimulus that does not usually provoke pain”, as opposed to hyperalgesia. The term “hyperalgesia” as used herein refers to increased pain from a stimulus that does usually provoke pain. Hyperalgesia may be induced by injury to a tissue or a nerve, resulting in an increased perception of pain by a patient. Injury-induced hyperalgesia can be divided into two subtypes: primary hyperalgesia (resulting in increased pain perception at a site local to the injury) and secondary hyperalgesia (pain is perceived in other areas of the body away from the injured site). Thus, in one embodiment bladder pain comprises allodynia or hyperalgesia. In one embodiment the nociceptive threshold of the patient is increased post administration of the clostridial neurotoxin using the method of the invention. In one embodiment the nociceptive threshold of the patient may be increased by at least 30, 40, 50, 60, 70 or 80% when compared to a patient that has not received a solution comprising a clostridial neurotoxin. In one embodiment the nociceptive threshold of the patient may be increased by 30-100%, 40-90%, 50-80% or 60-70% when compared to a patient that has not received administration of a solution comprising a clostridial neurotoxin. The term “nociceptive threshold” may refer to the level of noxious stimuli required for a patient to perceive pain. Further details of the clostridial neurotoxins embraced by the invention are provided below, together with technological background information. Bacteria in the genus Clostridia produce highly potent and specific protein toxins, which can poison neurons and other cells to which they are delivered. Examples of such clostridial   neurotoxins include the neurotoxins produced by C. tetani (TeNT) and by C. botulinum (BoNT) serotypes A-G, and X (see WO 2018/009903 A2), as well as those produced by C. baratii and C. butyricum. The clostridial neurotoxins are among some of the most potent toxins known. For example, botulinum neurotoxins have median lethal dose (LD ₅₀ ) values for mice ranging from 0.5 to 5 ng/kg, depending on the serotype. Both tetanus and botulinum neurotoxins act by inhibiting the function of affected neurons, specifically the release of neurotransmitters. While botulinum toxin acts at the neuromuscular junction and inhibits cholinergic transmission in the peripheral nervous system, tetanus toxin acts in the central nervous system. In nature, clostridial neurotoxins are synthesised as a single-chain polypeptide that is modified post-translationally by a proteolytic cleavage event to form two polypeptide chains joined together by a disulphide bond. Cleavage occurs at a specific cleavage site, often referred to as the activation site, that is located between the cysteine residues that provide the inter-chain disulphide bond. It is this di-chain form that is the active form of the toxin. The two chains are termed the heavy chain (H-chain), which has a molecular mass of approximately 100 kDa, and the light chain (L-chain), which has a molecular mass of approximately 50 kDa. The H-chain comprises an N-terminal translocation component (H _N domain) and a C-terminal targeting component (H _C domain). The cleavage site is located between the L-chain and the translocation domain components. Following binding of the H _C domain to its target neuron and internalisation of the bound toxin into the cell via an endosome, the H _N domain translocates the L-chain across the endosomal membrane and into the cytosol, and the L-chain provides a protease function (also known as a non-cytotoxic protease). Non-cytotoxic proteases act by proteolytically cleaving intracellular transport proteins known as SNARE proteins (e.g. SNAP-25, VAMP, or Syntaxin) – see Gerald K (2002) “Cell and Molecular Biology” (4th edition) John Wiley & Sons, Inc. The acronym SNARE derives from the term Soluble NSF Attachment Receptor, where NSF means N-ethylmaleimide-Sensitive Factor. SNARE proteins are integral to intracellular vesicle fusion, and thus to secretion of molecules via vesicle transport from a cell. The protease function is a zinc-dependent endopeptidase activity and exhibits a high substrate specificity for SNARE proteins. Accordingly, once delivered to a desired target cell, the non-cytotoxic protease is capable of inhibiting cellular secretion from the target cell. The L-chain proteases of clostridial neurotoxins are non-cytotoxic proteases that cleave SNARE proteins.   In view of the ubiquitous nature of SNARE proteins, clostridial neurotoxins such as botulinum neurotoxin have been successfully employed in a wide range of therapies. For example, William J. Lipham, Cosmetic and Clinical Applications of Botulinum Toxin (Slack, Inc., 2004) describes the use of clostridial neurotoxins, such as botulinum neurotoxins (BoNTs), BoNT/A, BoNT/B, BoNT/C ₁ , BoNT/D, BoNT/E, BoNT/F and BoNT/G, and tetanus neurotoxin (TeNT), to inhibit neuronal transmission in a wide variety of therapeutic and cosmetic applications - as an example, BOTOX ^TM is currently approved as a therapeutic for the following indications: for treating pain (see US 6,869,610, US 6,641,820, US 6,464,986, and US 6,113,915); for treating muscle injuries (see US 6,423,319); for treating sinus headache (see US 6,838,434); for treating neurological disorders such as Parkinson's disease (see US 6,620,415, US 6,306,403) and for treating neuropsychiatric disorders (see US 2004/0180061, US 2003/0211121). All of the above publications are hereby incorporated by reference in their entirety. Botulinum neurotoxin (BoNT) is produced by C. botulinum in the form of a large protein complex, consisting of BoNT itself complexed to a number of accessory proteins. There are at present nine different classes of botulinum neurotoxin, namely: botulinum neurotoxin serotypes A, B, C1, D, E, F, G, H, and X all of which share similar structures and modes of action. Different BoNT serotypes can be distinguished based on inactivation by specific neutralising anti-sera, with such classification by serotype correlating with percentage sequence identity at the amino acid level. BoNT proteins of a given serotype are further divided into different subtypes on the basis of amino acid percentage sequence identity. BoNTs are absorbed in the gastrointestinal tract, and, after entering the general circulation, bind to the presynaptic membrane of cholinergic nerve terminals and prevent the release of their neurotransmitter acetylcholine. BoNT/B, BoNT/D, BoNT/F and BoNT/G cleave synaptobrevin/vesicle-associated membrane protein (VAMP); BoNT/C1, BoNT/A and BoNT/E cleave the synaptosomal-associated protein of 25 kDa (SNAP-25); and BoNT/C1 cleaves syntaxin. BoNT/X has been found to cleave SNAP-25, VAMP1, VAMP2, VAMP3, VAMP4, VAMP5, Ykt6, and syntaxin 1. Tetanus toxin is produced in a single serotype by C. tetani. C. butyricum produces BoNT/E, while C. baratii produces BoNT/F.   Despite this diversity, BoNT/A remains the serotype of choice in therapy, with three commonly available commercial preparations (Botox®, Dysport® and Xeomin®), while only one BoNT/B product is available on the market (Neurobloc®/Myobloc®). To this day, these BoNT/A and BoNT/B products, which are toxins purified from clostridial strains, are the only two BoNT serotypes that are currently approved by regulatory agencies for use in humans for applications ranging, among others, from spasticity, bladder dysfunction, or hyperhidrosis (for BoNT/A) (see for example: https://www.medicines.org.uk/emc/medicine/112,https://www.me dicines.org.uk/emc/medicine /870, https://www.medicines.org.uk/emc/medicine/2162, herein incorporated by reference in their entirety) to cervical dystonia (for BoNT/B) (see for example, https://www.medicines.org.uk/emc/medicine/20568, herein incorporated by reference in its entirety). In contrast to a cytotoxic protease (e.g. ricin, diphtheria toxin, pseudomonas exotoxin), which acts by killing its natural target cell, clostridial neurotoxins are non-cytotoxic proteases acting by transiently incapacitating the cellular function of its natural target cell. Importantly, a non- cytotoxic protease does not kill the natural target cell upon which it acts. In addition to clostridial neurotoxins (e.g. botulinum neurotoxin, marketed under names such as Dysport ^TM , Neurobloc ^TM , and Botox ^TM ), some of the best known examples of non-cytotoxic proteases include IgA proteases (see, for example, WO99/032272), and antarease proteases (see, for example, WO2011/022357). The term “clostridial neurotoxin” encompasses any polypeptide produced by Clostridium bacteria that enters a neuron and inhibits neurotransmitter release, and such polypeptides produced by recombinant technologies or chemical techniques. For the purpose of the present invention, this term includes functionally equivalent non-cytotoxic proteases as noted above. Preferably, the clostridial neurotoxin is a botulinum neurotoxin (BoNT). An example of a BoNT/A neurotoxin amino acid sequence is provided as SEQ ID NO: 1, which is encoded by the nucleotide sequence provided as SEQ ID NO: 2. An example of a BoNT/B neurotoxin amino acid sequence is provided as SEQ ID NO: 3 (UniProt accession number B1INP5). An example of a BoNT/C neurotoxin amino acid sequence is provided as SEQ ID NO: 4 (UniProt accession number P18640). An example of a BoNT/D neurotoxin amino acid sequence is provided as SEQ ID NO: 5 (UniProt accession number P19321). An example of a BoNT/E neurotoxin amino acid sequence is provided as SEQ ID NO: 6 (accession number WP_003372387). An example of a BoNT/F neurotoxin amino acid sequence is provided as   SEQ ID NO: 7 (UniProt accession number Q57236) or as SEQ ID NO: 8 (UniProt/UniParc accession number UPI0001DE3DAC). An example of a BoNT/G neurotoxin amino acid sequence is provided as SEQ ID NO: 9 (accession number WP_039635782). An example of a BoNT/D-C neurotoxin amino acid sequence is provided as SEQ ID NO: 10 (accession number BAM65681). An example of a BoNT/X neurotoxin amino acid sequence is provided as SEQ ID NO: 12 (accession number BAQ12790.1). In one embodiment a BoNT of choice is BoNT/A, for example wild-type BoNT/A. The term “H _C domain” as used herein means a functionally distinct region of a neurotoxin heavy chain with a molecular weight of approximately 50 kDa that enables the binding of the neurotoxin to a receptor located on the surface of the target cell. The H _C domain consists of two structurally distinct subdomains, the “H _CN subdomain” (N-terminal part of the H _C domain) and the “H _CC subdomain” (C-terminal part of the H _C domain), each of which has a molecular weight of approximately 25 kDa. The term “LH _N domain” as used herein means a neurotoxin that is devoid of the H _C domain and consists of an endopeptidase domain (“L” or “light chain”) and the domain responsible for translocation of the endopeptidase into the cytoplasm (H _N domain of the heavy chain). As discussed above, clostridial neurotoxins are formed from two polypeptide chains, the heavy chain (H-chain), which has a molecular mass of approximately 100 kDa, and the light chain (L- chain), which has a molecular mass of approximately 50 kDa. The H-chain comprises a C- terminal targeting component (receptor binding domain or H _C domain) and an N-terminal translocation component (H _N domain). Examples of light chain reference sequences include: Botulinum type A neurotoxin: amino acid residues 1-448 Botulinum type B neurotoxin: amino acid residues 1-440 Botulinum type C1 neurotoxin: amino acid residues 1-441 Botulinum type D neurotoxin: amino acid residues 1-445 Botulinum type E neurotoxin: amino acid residues 1-422 Botulinum type F neurotoxin: amino acid residues 1-439 Botulinum type G neurotoxin: amino acid residues 1-441 Tetanus neurotoxin: amino acid residues 1-457   For recently-identified BoNT/X, the L-chain has been reported as corresponding to amino acids 1-439 thereof, with the L-chain boundary potentially varying by approximately 25 amino acids (e.g.1-414 or 1-464). The above-identified reference sequences should be considered a guide, as slight variations may occur according to sub-serotypes. By way of example, US 2007/0166332 (hereby incorporated by reference in its entirety) cites slightly different clostridial sequences: Botulinum type A neurotoxin: amino acid residues M1-K448 Botulinum type B neurotoxin: amino acid residues M1-K441 Botulinum type C1 neurotoxin: amino acid residues M1-K449 Botulinum type D neurotoxin: amino acid residues M1-R445 Botulinum type E neurotoxin: amino acid residues M1-R422 Botulinum type F neurotoxin: amino acid residues M1-K439 Botulinum type G neurotoxin: amino acid residues M1-K446 Tetanus neurotoxin: amino acid residues M1-A457 The term “activation loop” refers to a polypeptide domain comprising a proteolytic cleavage site. Activation loops of neurotoxins have been described in the art, such as in WO2016156113 (hereby incorporated by reference in its entirety). In one embodiment, the clostridial neurotoxin consists of or comprises an amino acid sequence having at least 70 %, preferably at least 75%, 80%, 85%, 90%, 95%, 99% or 100% sequence identity to any of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 12. In one embodiment, the clostridial neurotoxin consists of or comprises an amino acid sequence having at least 70 %, preferably at least 75%, 80%, 85%, 90%, 95%, 99% or 100% sequence identity to SEQ ID NO: 2. In one embodiment, the clostridial neurotoxin consists of or comprises an amino acid sequence of SEQ ID NO: 2 (e.g. BoNT/A). The term “clostridial neurotoxin” is also intended to embrace modified clostridial neurotoxins and derivatives thereof, including but not limited to those described below. A modified clostridial neurotoxin or derivative may contain one or more amino acids that has been modified   as compared to the native (unmodified) form of the clostridial neurotoxin, or may contain one or more inserted amino acids that are not present in the native (unmodified) form of the clostridial neurotoxin. By way of example, a modified clostridial neurotoxin may have modified amino acid sequences in one or more domains relative to the native (unmodified) clostridial neurotoxin sequence. Such modifications may modify functional aspects of the toxin, for example biological activity or persistence. A preferred modified BoNT/A is one that comprises a modification at one or more amino acid residue(s) selected from: ASN 886, ASN 905, GLN 915, ASN 918, GLU 920, ASN 930, ASN 954, SER 955, GLN 991, GLU 992, GLN 995, ASN 1006, ASN 1025, ASN 1026, ASN 1032, ASN 1043, ASN 1046, ASN 1052, ASP 1058, HIS 1064, ASN 1080, GLU 1081, GLU 1083, ASP 1086, ASN 1188, ASP 1213, GLY 1215, ASN 1216, GLN 1229, ASN 1242, ASN 1243, SER 1274, and THR 1277. Such modified BoNT/A demonstrates a reduction in, or absence of, side effects compared to the use of known BoNT/A. The increased tissue retention properties of the modified BoNT/A of the invention also provides increased potency and/or duration of action and can allow for reduced dosages to be used compared to known clostridial toxin therapeutics (or increased dosages without any additional adverse effects), thus providing further advantages. The modification may be a modification when compared to unmodified BoNT/A shown as SEQ ID NO: 2, wherein the amino acid residue numbering is determined by alignment with SEQ ID NO: 2. As the presence of a methionine residue at position 1 of SEQ ID NO: 2 (as well as the SEQ ID NOs corresponding to modified BoNT/A polypeptides described herein) is optional, the skilled person will take the presence/absence of the methionine residue into account when determining amino acid residue numbering. For example, where SEQ ID NO: 2 includes a methionine, the position numbering will be as defined above (e.g. ASN 886 will be ASN 886 of SEQ ID NO: 2). Alternatively, where the methionine is absent from SEQ ID NO: 2 the amino acid residue numbering should be modified by -1 (e.g. ASN 886 will be ASN 885 of SEQ ID NO: 2). Similar considerations apply when the methionine at position 1 of the other polypeptide sequences described herein is present/absent, and the skilled person will readily determine the correct amino acid residue numbering using techniques routine in the art. The amino acid residue(s) indicated for modification are surface exposed amino acid residue(s).   A modified BoNT/A may comprise a modification at one or more amino acid residue(s) selected from: ASN 886, ASN 930, ASN 954, SER 955, GLN 991, ASN 1025, ASN 1026, ASN 1052, ASN 1188, ASP 1213, GLY 1215, ASN 1216, GLN 1229, ASN 1242, ASN 1243, SER 1274 and THR 1277. The modified BoNT/A may be encoded by a nucleic acid sequence having at least 70% sequence identity to a nucleic acid sequence selected from SEQ ID NOs: 13, 15, 17, and 19. For example, a nucleic acid sequence having at least 80%, 90%, 95% or 99.9% sequence identity to a nucleic acid sequence selected from SEQ ID NOs: 13, 15, 17, and 19. Preferably, a modified BoNT/A for use in the invention may be encoded by a nucleic acid comprising (or consisting of) SEQ ID NO: 13, 15, 17, and 19. The modified BoNT/A may comprise a polypeptide sequence having at least 70% sequence identity to a polypeptide sequence selected from SEQ ID NOs: 14, 16, 18, and 20. For example, a polypeptide sequence having at least 80%, 90%, 95% or 99.9% sequence identity to a polypeptide sequence selected from SEQ ID NOs: 14, 16, 18, and 20. Preferably, a modified BoNT/A for use in the invention may comprise (more preferably consist of) a polypeptide sequence selected from SEQ ID NOs: 14, 16, 18, and 20. The term “one or more amino acid residue(s)” when used in the context of modified BoNT/A preferably means at least 2, 3, 4, 5, 6 or 7 of the indicated amino acid residue(s). Thus, a modified BoNT/A may comprise at least 2, 3, 4, 5, 6 or 7 (preferably 7) modifications at the indicated amino acid residue(s). A modified BoNT/A may comprise 1-30, 3-20, or 5-10 amino acid modifications. More preferably, the term “one or more amino acid residue(s)” when used in the context of modified BoNT/A means all of the indicated amino acid residue(s). Preferably, beyond the one or more amino acid modification(s) at the indicated amino acid residue(s), the modified BoNT/A does not contain any further amino acid modifications when compared to SEQ ID NO: 2. Most preferably, a modified BoNT/A comprises (more preferably consists of) a modification at one or more amino acid residue(s) selected from: ASN 886, ASN 930, SER 955, GLN 991, ASN 1026, ASN 1052, and GLN 1229. The modified BoNT/A may be encoded by a nucleic acid sequence having at least 70% sequence identity to SEQ ID NO: 13. For example, a nucleic acid sequence having at least 80%, 90%, 95% or 99.9% sequence identity to SEQ ID NO: 13. Preferably, a modified BoNT/A for use in the invention may be encoded by a nucleic acid comprising (or consisting of) SEQ ID NO: 13. The modified BoNT/A may comprise a polypeptide sequence having at least 70% sequence identity to SEQ ID NO: 14. For example, a polypeptide sequence having at least 80%, 90%, 95% or 99.9% sequence identity to SEQ   ID NO: 14. Preferably, a modified BoNT/A for use in the invention may comprise (more preferably consist of) SEQ ID NO: 14. The modification may be selected from: i. substitution of an acidic surface exposed amino acid residue with a basic amino acid residue; ii. substitution of an acidic surface exposed amino acid residue with an uncharged amino acid residue; iii. substitution of an uncharged surface exposed amino acid residue with a basic amino acid residue; iv. insertion of a basic amino acid residue; and v. deletion of an acidic surface exposed amino acid residue. A modification as indicated above results in a modified BoNT/A that has an increased positive surface charge and increased isoelectric point when compared to the corresponding unmodified BoNT/A. The isoelectric point (pI) is a specific property of a given protein. As is well known in the art, proteins are made from a specific sequence of amino acids (also referred to when in a protein as amino acid residues). Each amino acid of the standard set of twenty has a different side chain (or R group), meaning that each amino acid residue in a protein displays different chemical properties such as charge and hydrophobicity. These properties may be influenced by the surrounding chemical environment, such as the temperature and pH. The overall chemical characteristics of a protein will depend on the sum of these various factors. Certain amino acid residues (detailed below) possess ionisable side chains that may display an electric charge depending on the surrounding pH. Whether such a side chain is charged or not at a given pH depends on the pKa of the relevant ionisable moiety, wherein pKa is the negative logarithm of the acid dissociation constant (Ka) for a specified proton from a conjugate base. For example, acidic residues such as aspartic acid and glutamic acid have side chain carboxylic acid groups with pKa values of approximately 4.1 (precise pKa values may depend on temperature, ionic strength and the microenvironment of the ionisable group). Thus, these side chains exhibit a negative charge at a pH of 7.4 (often referred to as “physiological pH”). At low pH values, these side chains will become protonated and lose their charge.   Conversely, basic residues such as lysine and arginine have nitrogen-containing side chain groups with pKa values of approximately 10-12. These side chains therefore exhibit a positive charge at a pH of 7.4. These side chains will become de-protonated and lose their charge at high pH values. The overall (net) charge of a protein molecule therefore depends on the number of acidic and basic residues present in the protein (and their degree of surface exposure) and on the surrounding pH. Changing the surrounding pH changes the overall charge on the protein. Accordingly, for every protein there is a given pH at which the number of positive and negative charges is equal and the protein displays no overall net charge. This point is known as the isoelectric point (pI). The isoelectric point is a standard concept in protein biochemistry with which the skilled person would be familiar. The isoelectric point (pI) is therefore defined as the pH value at which a protein displays a net charge of zero. An increase in pI means that a higher pH value is required for the protein to display a net charge of zero. Thus, an increase in pI represents an increase in the net positive charge of a protein at a given pH. Conversely, a decrease in pI means that a lower pH value is required for the protein to display a net charge of zero. Thus, a decrease in pI represents a decrease in the net positive charge of a protein at a given pH. Methods of determining the pI of a protein are known in the art and would be familiar to a skilled person. By way of example, the pI of a protein can be calculated from the average pKa values of each amino acid present in the protein (“calculated pI”). Such calculations can be performed using computer programs known in the art, such as the Compute pI/MW Tool from ExPASy (https://web.expasy.org/compute_pi/), which is the preferred method for calculating pI in accordance with the present invention. Comparisons of pI values between different molecules should be made using the same calculation technique/program. Where appropriate, the calculated pI of a protein can be confirmed experimentally using the technique of isoelectric focusing (“observed pI”). This technique uses electrophoresis to separate proteins according to their pI. Isoelectric focusing is typically performed using a gel that has an immobilised pH gradient. When an electric field is applied, the protein migrates through the pH gradient until it reaches the pH at which it has zero net charge, this point being the pI of the protein. Results provided by isoelectric focusing are typically relatively low-   resolution in nature, and thus the present inventors believe that results provided by calculated pI (as described above) are more appropriate to use. Throughout the present specification, “pI” means “calculated pI” unless otherwise stated. The pI of a protein may be increased or decreased by altering the number of basic and/or acidic groups displayed on its surface. This can be achieved by modifying one or more amino acids of the protein. For example, an increase in pI may be provided by reducing the number of acidic residues, or by increasing the number of basic residues. A modified BoNT/A of the invention may have a pI value that is at least 0.2, 0.4, 0.5 or 1 pI units higher than that of an unmodified BoNT/A (e.g. SEQ ID NO: 2). Preferably, a modified BoNT/A may have a pI of at least 6.6, e.g. at least 6.8. The properties of the 20 standard amino acids are indicated in the table below:   The following amino acids are considered charged amino acids: aspartic acid (negative), glutamic acid (negative), arginine (positive), and lysine (positive). At a pH of 7.4, the side chains of aspartic acid (pKa 3.1) and glutamic acid (pKa 4.1) have a negative charge, while the side chains of arginine (pKa 12.5) and lysine (pKa 10.8) have a positive charge. Aspartic acid and glutamic acid are referred to as acidic amino acid residues. Arginine and lysine are referred to as basic amino acid residues. The following amino acids are considered uncharged, polar (meaning they can participate in hydrogen bonding) amino acids: asparagine, glutamine, histidine, serine, threonine, tyrosine, cysteine, methionine, and tryptophan. The following amino acids are considered uncharged, hydrophobic amino acids: alanine, valine, leucine, isoleucine, phenylalanine, proline, and glycine. In an amino acid insertion, an additional amino acid residue (one that is not normally present) is incorporated into the BoNT/A polypeptide sequence, thus increasing the total number of amino acid residues in said sequence. In an amino acid deletion, an amino acid residue is removed from the clostridial toxin amino acid sequence, thus reducing the total number of amino acid residues in said sequence. Preferably, the modification is a substitution, which advantageously maintains the same number of amino acid residues in the modified BoNT/A. In an amino acid substitution, an amino acid residue that forms part of the BoNT/A polypeptide sequence is replaced with a different amino acid residue. The replacement amino acid residue may be one of the 20 standard amino acids, as described above. Alternatively, the replacement amino acid in an amino acid substitution may be a non-standard amino acid (an amino acid that is not part of the standard set of 20 described above). By way of example, the replacement amino acid may be a basic non-standard amino acid, e.g. L-Ornithine, L-2-amino-3-guanidinopropionic acid, or D-isomers of Lysine, Arginine and Ornithine). Methods for introducing non-standard amino acids into proteins are known in the art and include recombinant protein synthesis using E. coli auxotrophic expression hosts. In one embodiment, the substitution is selected from: substitution of an acidic amino acid residue with a basic amino acid residue, substitution of an acidic amino acid residue with an uncharged amino acid residue, and substitution of an uncharged amino acid residue with a   basic amino acid residue. In one embodiment, wherein the substitution is a substitution of an acidic amino acid residue with an uncharged amino acid residue, the acidic amino acid residue is replaced with its corresponding uncharged amide amino acid residue (i.e. aspartic acid is replaced with asparagine, and glutamic acid is replaced with glutamine). Preferably, the basic amino acid residue is a lysine residue or an arginine residue. In other words, the substitution is substitution with lysine or arginine. Most preferably, the modification is substitution with lysine. A Translocation Domain is a molecule that enables translocation of a protease into a target cell such that a functional expression of protease activity occurs within the cytosol of the target cell. Whether any molecule (e.g. a protein or peptide) possesses the requisite translocation function of the present invention may be confirmed by any one of a number of conventional assays. For example, Shone C. (1987) describes an in vitro assay employing liposomes, which are challenged with a test molecule. Presence of the requisite translocation function is confirmed by release from the liposomes of K ⁺ and/ or labelled NAD, which may be readily monitored [see Shone C. (1987) Eur. J. Biochem; vol.167(1): pp.175-180]. A further example is provided by Blaustein R. (1987), which describes a simple in vitro assay employing planar phospholipid bilayer membranes. The membranes are challenged with a test molecule and the requisite translocation function is confirmed by an increase in conductance across said membranes [see Blaustein (1987) FEBS Letts; vol.226, no.1: pp. 115-120]. Additional methodology to enable assessment of membrane fusion and thus identification of Translocation Domains suitable for use in the present invention are provided by Methods in Enzymology Vol 220 and 221, Membrane Fusion Techniques, Parts A and B, Academic Press 1993. The present invention also embraces variant translocation domains, so long as the variant domains still demonstrate the requisite translocation activity. By way of example, a variant may have at least 70%, preferably at least 80%, more preferably at least 90%, and most preferably at least 95% or at least 98% amino acid sequence homology with a reference translocation domain. The term fragment, when used in relation to a translocation domain, means a peptide   having at least 20, preferably at least 40, more preferably at least 80, and most preferably at least 100 amino acid residues of the reference translocation domain. In the case of a clostridial translocation domain, the fragment preferably has at least 100, preferably at least 150, more preferably at least 200, and most preferably at least 250 amino acid residues of the reference translocation domain (e.g. H _N domain). Translocation ‘fragments’ of the present invention embrace fragments of variant translocation domains based on the reference sequences. The Translocation Domain is preferably capable of formation of ion-permeable pores in lipid membranes under conditions of low pH. Preferably it has been found to use only those portions of the protein molecule capable of pore-formation within the endosomal membrane. The Translocation Domain may be obtained from a microbial protein source, in particular from a bacterial or viral protein source. Hence, in one embodiment, the Translocation Domain is a translocating domain of an enzyme, such as a bacterial toxin or viral protein. It is well documented that certain domains of bacterial toxin molecules are capable of forming such pores. It is also known that certain translocation domains of virally expressed membrane fusion proteins are capable of forming such pores. Such domains may be employed in the present invention. The Translocation Domain may be of a clostridial origin, such as the H _N domain (or a functional component thereof). H _N means a portion or fragment of the H-chain of a clostridial neurotoxin approximately equivalent to the amino-terminal half of the H-chain, or the domain corresponding to that fragment in the intact H-chain. Examples of suitable (reference) Translocation Domains include: Botulinum type A neurotoxin - amino acid residues (449-871) Botulinum type B neurotoxin - amino acid residues (441-858) Botulinum type C neurotoxin - amino acid residues (442-866) Botulinum type D neurotoxin - amino acid residues (446-862) Botulinum type E neurotoxin - amino acid residues (423-845) Botulinum type F neurotoxin - amino acid residues (440-864) Botulinum type G neurotoxin - amino acid residues (442-863) Tetanus neurotoxin - amino acid residues (458-879)   The above-identified reference sequence should be considered a guide as slight variations may occur according to sub-serotypes. By way of example, US 2007/0166332 (hereby incorporated by reference thereto) cites slightly different clostridial sequences: Botulinum type A neurotoxin - amino acid residues (A449-K871) Botulinum type B neurotoxin - amino acid residues (A442-S858) Botulinum type C neurotoxin - amino acid residues (T450-N866) Botulinum type D neurotoxin - amino acid residues (D446-N862) Botulinum type E neurotoxin - amino acid residues (K423-K845) Botulinum type F neurotoxin - amino acid residues (A440-K864) Botulinum type G neurotoxin - amino acid residues (S447-S863) Tetanus neurotoxin - amino acid residues (S458-V879) In the context of the present invention, a variety of clostridial neurotoxin H _N regions comprising a translocation domain can be useful in aspects of the present invention with the proviso that these active fragments can facilitate the release of a non-cytotoxic protease (e.g. a clostridial L-chain) from intracellular vesicles into the cytoplasm of the target cell and thus participate in executing the overall cellular mechanism whereby a clostridial neurotoxin proteolytically cleaves a substrate. The H _N regions from the heavy chains of clostridial neurotoxins are approximately 410-430 amino acids in length and comprise a translocation domain. Research has shown that the entire length of a H _N region from a clostridial neurotoxin heavy chain is not necessary for the translocating activity of the translocation domain. Thus, aspects of this embodiment can include clostridial neurotoxin H _N regions comprising a translocation domain having a length of, for example, at least 350 amino acids, at least 375 amino acids, at least 400 amino acids and at least 425 amino acids. Other aspects of this embodiment can include clostridial neurotoxin H _N regions comprising translocation domain having a length of, for example, at most 350 amino acids, at most 375 amino acids, at most 400 amino acids and at most 425 amino acids. For further details on the genetic basis of toxin production in Clostridium botulinum and C. tetani, we refer to Henderson et al (1997) in The Clostridia: Molecular Biology and Pathogenesis, Academic press. The term H _N embraces naturally-occurring neurotoxin H _N portions, and modified H _N portions having amino acid sequences that do not occur in nature and/ or synthetic amino acid residues,   so long as the modified H _N portions still demonstrate the above-mentioned translocation function. Alternatively, the Translocation Domain may be of a non-clostridial origin. Examples of non- clostridial (reference) Translocation Domain origins include, but not be restricted to, the translocation domain of diphtheria toxin [O’Keefe et al., Proc. Natl. Acad. Sci. USA (1992) 89, 6202-6206; Silverman et al., J. Biol. Chem. (1993) 269, 22524-22532; and London, E. (1992) Biochem. Biophys. Acta., 1112, pp.25-51], the translocation domain of Pseudomonas exotoxin type A [Prior et al. Biochemistry (1992) 31, 3555-3559], the translocation domains of anthrax toxin [Blanke et al. Proc. Natl. Acad. Sci. USA (1996) 93, 8437-8442], a variety of fusogenic or hydrophobic peptides of translocating function [Plank et al. J. Biol. Chem. (1994) 269, 12918- 12924; and Wagner et al (1992) PNAS, 89, pp.7934-7938], and amphiphilic peptides [Murata et al (1992) Biochem., 31, pp.1986-1992]. The Translocation Domain may mirror the Translocation Domain present in a naturally-occurring protein, or may include amino acid variations so long as the variations do not destroy the translocating ability of the Translocation Domain. Examples of clostridial neurotoxin H _C domain reference sequences include: BoNT/A - N872-L1296 BoNT/B - E859-E1291 BoNT/C1 - N867-E1291 BoNT/D - S863-E1276 BoNT/E - R846-K1252 BoNT/F - K865-E1274 BoNT/G - N864-E1297 TeNT - I880-D1315 For recently-identified BoNT/X, the H _C domain has been reported as corresponding to amino acids 893-1306 thereof, with the domain boundary potentially varying by approximately 25 amino acids (e.g.868-1306 or 918-1306). The clostridial neurotoxins described herein may further comprise a translocation facilitating domain. Said domain facilitates delivery of the non-cytotoxic protease into the cytosol of the target cell and are described, for example, in WO 08/008803 and WO 08/008805, each of which is herein incorporated by reference thereto.   By way of example, suitable translocation facilitating domains include an enveloped virus fusogenic peptide domain, for example, suitable fusogenic peptide domains include influenzavirus fusogenic peptide domain (e.g. influenza A virus fusogenic peptide domain of 23 amino acids), alphavirus fusogenic peptide domain (e.g. Semliki Forest virus fusogenic peptide domain of 26 amino acids), vesiculovirus fusogenic peptide domain (e.g. vesicular stomatitis virus fusogenic peptide domain of 21 amino acids), respirovirus fusogenic peptide domain (e.g. Sendai virus fusogenic peptide domain of 25 amino acids), morbiliivirus fusogenic peptide domain (e.g. Canine distemper virus fusogenic peptide domain of 25 amino acids), avulavirus fusogenic peptide domain (e.g. Newcastle disease virus fusogenic peptide domain of 25 amino acids), henipavirus fusogenic peptide domain (e.g. Hendra virus fusogenic peptide domain of 25 amino acids), metapneumovirus fusogenic peptide domain (e.g. Human metapneumovirus fusogenic peptide domain of 25 amino acids) or spumavirus fusogenic peptide domain such as simian foamy virus fusogenic peptide domain; or fragments or variants thereof. By way of further example, a translocation facilitating domain may comprise a clostridial neurotoxin H _CN domain or a fragment or variant thereof. In more detail, a clostridial neurotoxin H _CN translocation facilitating domain may have a length of at least 200 amino acids, at least 225 amino acids, at least 250 amino acids, at least 275 amino acids. In this regard, a clostridial neurotoxin H _CN translocation facilitating domain preferably has a length of at most 200 amino acids, at most 225 amino acids, at most 250 amino acids, or at most 275 amino acids. Specific (reference) examples include: Botulinum type A neurotoxin - amino acid residues (872-1110) Botulinum type B neurotoxin - amino acid residues (859-1097) Botulinum type C neurotoxin - amino acid residues (867-1111) Botulinum type D neurotoxin - amino acid residues (863-1098) Botulinum type E neurotoxin - amino acid residues (846-1085) Botulinum type F neurotoxin - amino acid residues (865-1105) Botulinum type G neurotoxin - amino acid residues (864-1105) Tetanus neurotoxin - amino acid residues (880-1127) The above sequence positions may vary a little according to serotype/ sub-type, and further examples of suitable (reference) clostridial neurotoxin H _CN domains include:   Botulinum type A neurotoxin - amino acid residues (874-1110) Botulinum type B neurotoxin - amino acid residues (861-1097) Botulinum type C neurotoxin - amino acid residues (869-1111) Botulinum type D neurotoxin - amino acid residues (865-1098) Botulinum type E neurotoxin - amino acid residues (848-1085) Botulinum type F neurotoxin - amino acid residues (867-1105) Botulinum type G neurotoxin - amino acid residues (866-1105) Tetanus neurotoxin - amino acid residues (882-1127) Any of the above-described facilitating domains may be combined with any of the previously described translocation domain peptides that are suitable for use in the present invention. Thus, by way of example, a non-clostridial facilitating domain may be combined with non- clostridial translocation domain peptide or with clostridial translocation domain peptide. Alternatively, a clostridial neurotoxin H _CN translocation facilitating domain may be combined with a non-clostridial translocation domain peptide. Alternatively, a clostridial neurotoxin H _CN facilitating domain may be combined or with a clostridial translocation domain peptide, examples of which include: Botulinum type A neurotoxin - amino acid residues (449-1110) Botulinum type B neurotoxin - amino acid residues (442-1097) Botulinum type C neurotoxin - amino acid residues (450-1111) Botulinum type D neurotoxin - amino acid residues (446-1098) Botulinum type E neurotoxin - amino acid residues (423-1085) Botulinum type F neurotoxin - amino acid residues (440-1105) Botulinum type G neurotoxin - amino acid residues (447-1105) Tetanus neurotoxin - amino acid residues (458-1127) The H _C peptide of a native clostridial neurotoxin comprises approximately 400-440 amino acid residues, and consists of two functionally distinct domains of approximately 25kDa each, namely the N-terminal region (commonly referred to as the H _CN peptide or domain) and the C- terminal region (commonly referred to as the H _CC peptide or domain). This fact is confirmed by the following publications, each of which is herein incorporated in its entirety by reference thereto: Umland TC (1997) Nat. Struct. Biol.4: 788-792; Herreros J (2000) Biochem. J.347: 199-204; Halpern J (1993) J. Biol. Chem.268: 15, pp.11188-11192; Rummel A (2007) PNAS 104: 359-364; Lacey DB (1998) Nat. Struct. Biol.5: 898-902; Knapp (1998) Am. Cryst. Assoc. Abstract Papers 25: 90; Swaminathan and Eswaramoorthy (2000) Nat. Struct. Biol.7: 1751-   1759; and Rummel A (2004) Mol. Microbiol. 51(3), 631-643. Moreover, it has been well documented that the C-terminal region (H _CC ), which constitutes the C-terminal 160-200 amino acid residues, is responsible for binding of a clostridial neurotoxin to its natural cell receptors, namely to nerve terminals at the neuromuscular junction - this fact is also confirmed by the above publications. Example clostridial H _CC reference sequences are presented below: Botulinum type A neurotoxin - amino acid residues (Y1111-L1296) Botulinum type B neurotoxin - amino acid residues (Y1098-E1291) Botulinum type C neurotoxin - amino acid residues (Y1112-E1291) Botulinum type D neurotoxin - amino acid residues (Y1099-E1276) Botulinum type E neurotoxin - amino acid residues (Y1086-K1252) Botulinum type F neurotoxin - amino acid residues (Y1106-E1274) Botulinum type G neurotoxin - amino acid residues (Y1106-E1297) Tetanus neurotoxin - amino acid residues (Y1128-D1315). The above-identified reference sequences should be considered a guide as slight variations may occur according to sub-serotypes. A modified clostridial neurotoxin may have one or more modifications in the amino acid sequence of the heavy chain (such as a modified H _C domain), wherein said modified heavy chain binds to target nerve cells with a higher or lower affinity than the native (unmodified) clostridial neurotoxin. Such modifications in the H _C domain can include modifying residues in the ganglioside binding site of the H _C domain or in the protein (SV2 or synaptotagmin) binding site that alter binding to the ganglioside receptor and/or the protein receptor of the target nerve cell. Examples of such modified clostridial neurotoxins are described in WO 2006/027207 and WO 2006/114308, both of which are hereby incorporated by reference in their entirety. A modified clostridial neurotoxin may have one or more modifications in the amino acid sequence of the light chain, for example modifications in the substrate binding or catalytic domain which may alter or modify the SNARE protein specificity of the modified L-chain. Examples of such modified clostridial neurotoxins are described in WO 2010/120766 and US 2011/0318385, both of which are hereby incorporated by reference in their entirety.   Thus, the term “clostridial neurotoxin” is intended to embrace hybrid and chimeric clostridial neurotoxins. In one embodiment a modified clostridial neurotoxin may be a hybrid or chimeric clostridial neurotoxin with the proviso that said clostridial neurotoxin comprises a modified BoNT/A H _CC domain of the invention. A hybrid clostridial neurotoxin comprises at least a portion of a light chain from one clostridial neurotoxin or subtype thereof, and at least a portion of a heavy chain from another clostridial neurotoxin or clostridial neurotoxin subtype. In one embodiment the hybrid clostridial neurotoxin may contain the entire light chain from one clostridial neurotoxin subtype and the heavy chain from another clostridial neurotoxin subtype. In one embodiment, a chimeric clostridial neurotoxin may contain a portion (e.g. the binding domain) of the heavy chain of one clostridial neurotoxin subtype, with another portion of the heavy chain being from another clostridial neurotoxin subtype. Similarly or alternatively, the therapeutic element may comprise light chain portions from different clostridial neurotoxins. Such hybrid or chimeric clostridial neurotoxins are useful, for example, as a means of delivering the therapeutic benefits of such clostridial neurotoxins to patients who are immunologically resistant to a given clostridial neurotoxin subtype, to patients who may have a lower than average concentration of receptors to a given clostridial neurotoxin heavy chain binding domain, or to patients who may have a protease-resistant variant of the membrane or vesicle toxin substrate (e.g., SNAP-25, VAMP and syntaxin). Hybrid and chimeric clostridial neurotoxins are described in US 8,071,110, which publication is hereby incorporated by reference in its entirety. For example, the chimeric neurotoxin may comprise a LH _N domain from a first neurotoxin covalently linked to a H _C domain from a second neurotoxin, preferably wherein said first and second neurotoxins are different, wherein the C-terminal amino acid residue of said LH _N domain corresponds to the first amino acid residue of the 3 ₁₀ helix separating the LH _N and H _C domains in said first neurotoxin, and wherein the N-terminal amino acid residue of said H _C domain corresponds to the second amino acid residue of the 3 ₁₀ helix separating the LH _N and H _C domains in said second neurotoxin. In one embodiment, the clostridial neurotoxin is a chimeric neurotoxin which comprises an H _C domain from a BoNT/B and an LH _N domain from a BoNT/A, BoNT/C, BoNT/D, BoNT/E, BoNT/F, BoNT/G or BoNT/X. For example, in one embodiment, the H _C domain consists of or comprises an amino acid sequence corresponding to amino acid residues 860 to 1291 of SEQ ID NO: 3 (e.g. BoNT/B), or an amino acid sequence having at least 70 %, preferably at least 75%, 80%, 85%, 90%,   95% or 99% sequence identity thereto, and the LH _N domain consists of or comprises an amino acid sequence selected from the group consisting of: ‐ amino acid residues 1 to 872 of SEQ ID NO: 2 (e.g. BoNT/A), or a sequence having at least 70 %, preferably at least 75%, 80%, 85%, 90%, 95% or 99% sequence identity thereto, ‐ amino acid residues 1 to 867 of SEQ ID NO: 4, or a sequence having at least 70 %, preferably at least 75%, 80%, 85%, 90%, 95% or 99% sequence identity thereto, ‐ amino acid residues 1 to 863 of SEQ ID NO: 5, or a sequence having at least 70 %, preferably at least 75%, 80%, 85%, 90%, 95% or 99% sequence identity thereto, ‐ amino acid residues 1 to 846 of SEQ ID NO: 6, or a sequence having at least 70 %, preferably at least 75%, 80%, 85%, 90%, 95% or 99% sequence identity thereto, ‐ amino acid residues 1 to 865 of SEQ ID NO: 7, or a sequence having at least 70 %, preferably at least 75%, 80%, 85%, 90%, 95% or 99% sequence identity thereto, ‐ amino acid residues 1 to 862 of SEQ ID NO: 8, or a sequence having at least 70 %, preferably at least 75%, 80%, 85%, 90%, 95% or 99% sequence identity thereto, and ‐ amino acid residues 1 to 864 of SEQ ID NO: 9, or a sequence having at least 70 %, preferably at least 75%, 80%, 85%, 90%, 95% or 99% sequence identity thereto, ‐ amino acid residues 1 to 863 of SEQ ID NO: 10, or a sequence having at least 70 %, preferably at least 75%, 80%, 85%, 90%, 95% or 99% sequence identity thereto. In one embodiment, a clostridial neurotoxin is BoNT/X comprising at least one domain from a non-BoNT/X clostridial neurotoxin (e.g. a BoNT/X hybrid or chimera). For example, in one embodiment a clostridial neurotoxin may comprise: i. A BoNT/X L-chain and a non-BoNT/X H _N and H _C domain; ii. A BoNT/X H _N domain and a non-BoNT/X L-chain and H _C domain iii. A BoNT/X H _C domain and a non-BoNT/X L-chain and H _N domain; iv. A BoNT/X L-chain and H _N domain and a non-BoNT/X H _C domain v. A BoNT/X L-chain and H _C domain and a non-BoNT/X H _N domain; or vi. A BoNT/X H _N domain and H _C domain and a non-BoNT/X L-chain. In a preferred embodiment, the clostridial neurotoxin is a chimeric neurotoxin which comprises an H _C domain from a BoNT/B and an LH _N domain from a BoNT/A. In a more preferred embodiment, the H _C domain consists of or comprises an amino acid sequence corresponding to amino acid residues 860 to 1291 of SEQ ID NO: 3, or an amino acid sequence having at least 70%, preferably at least 75%, 80%, 85%, 90%, 95% or 99%   sequence identity thereto, and the LH _N domain comprises an amino acid sequence corresponding to amino acid residues 1 to 872 of SEQ ID NO: 2, or an amino acid sequence having at least 70%, preferably at least 75%, 80%, 85%, 90%, 95% or 99% sequence identity thereto. In embodiments where the clostridial neurotoxin comprises an H _C domain from a BoNT/B (for example, where the clostridial neurotoxin is BoNT/B, or a chimeric neurotoxin which comprises an H _C domain from a BoNT/B), the clostridial neurotoxin may have one or more modifications in the amino acid sequence of the heavy chain (such as in the H _C domain) providing a “modified heavy chain”, preferably wherein said modified heavy chain binds to target nerve cells with a higher (or lower) affinity than the native neurotoxin. Such modifications in the H _C domain can include modifications of amino acid residues in the ganglioside binding site of the H _CC domain that can alter binding to the ganglioside of the target nerve cell, and/or modifications of amino acid residues in the protein receptor binding site of the H _CC domain that can alter binding to the protein receptor of the target nerve cell. Examples of such modified neurotoxins are described in WO2006027207 and WO2006114308, both of which are hereby incorporated by reference in their entirety. In one embodiment, the clostridial neurotoxin of the present invention can be both chimeric and modified, as described above. For example, in a preferred embodiment, the clostridial neurotoxin comprises (or consists of) the amino acid sequence SEQ ID NO: 11, or an amino acid sequence having at least 70%, preferably at least 75%, 80%, 85%, 90%, 95% or 99% sequence identity thereto. In one embodiment, the clostridial neurotoxin of the present invention can be both chimeric and modified, as described above. For example, in a preferred embodiment, the clostridial neurotoxin comprises (or consists of) the amino acid sequence SEQ ID NO: 11 (e.g. BoNT/AB _MY ), or an amino acid sequence having at least 70%, preferably at least 75%, 80%, 85%, 90%, 95% or 99% sequence identity thereto. The term “clostridial neurotoxin” may also embrace newly discovered botulinum neurotoxin protein family members expressed by non-clostridial microorganisms, such as the Enterococcus encoded toxin which has closest sequence identity to BoNT/X, the Weissella oryzae encoded toxin called BoNT/Wo (NCBI Ref Seq: WP_027699549.1), which cleaves VAMP2 at W89-W90, the Enterococcus faecium encoded toxin (GenBank: OTO22244.1),   which cleaves VAMP2 and SNAP25, and the Chryseobacterium pipero encoded toxin (NCBI Ref.Seq: WP_034687872.1). The term “clostridial neurotoxin” is intended to embrace re-targeted clostridial neurotoxins. In a re-targeted clostridial neurotoxin, the clostridial neurotoxin is modified to include an exogenous ligand known as a Targeting Moiety (TM). The TM is selected to provide binding specificity for a desired target cell, and as part of the re-targeting process the native binding portion of the clostridial neurotoxin (e.g. the H _C domain, or the H _CC domain) may be removed. The term “clostridial neurotoxin” may embrace catalytically inactive clostridial neurotoxins. The term “catalytically inactive” as used herein in respect of a clostridial neurotoxin L-chain means that said L-chain exhibits substantially no non-cytotoxic protease activity, preferably the term “catalytically inactive” as used herein in respect of a clostridial neurotoxin L-chain means that said L-chain exhibits no non-cytotoxic protease activity. In one embodiment, a catalytically inactive clostridial neurotoxin L-chain is one that does not cleave a protein of the exocytic fusion apparatus in a target cell. The term “substantially no non-cytotoxic protease activity” means that the clostridial neurotoxin L-chain has less than 5% of the non-cytotoxic protease activity of a catalytically active clostridial neurotoxin L-chain, for example less than 2%, 1% or preferably less than 0.1% of the non-cytotoxic protease activity of a catalytically active clostridial neurotoxin L-chain. Non-cytotoxic protease activity can be determined in vitro by incubating a test clostridial neurotoxin L-chain with a SNARE protein and comparing the amount of SNARE protein cleaved by the test clostridial neurotoxin L-chain when compared to the amount of SNARE protein cleaved by a catalytically active clostridial neurotoxin L-chain under the same conditions. Routine techniques, such as SDS-PAGE and Western blotting can be used to quantify the amount of SNARE protein cleaved. Suitable in vitro assays are described in WO 2019/145577 A1, which is incorporated herein by reference. The present invention also embraces clostridial neurotoxins that have a non-native protease cleavage site. In such clostridial neurotoxins, the native protease cleavage site (also known as the activation site, as described above) is modified or replaced with a protease cleavage site that is not native to that clostridial neurotoxin (i.e. an exogenous cleavage site). Such a site will require an exogenous protease for cleavage, which allows for improved control over the timing and location of cleavage events. Non-native protease cleavage sites that may be employed in clostridial neurotoxins include: TEV(Tobacco Etch virus) (ENLYFQ↓G) (SEQ ID NO: 26) Thrombin (LVPR↓GS) (SEQ ID NO: 27)   PreScission (LEVLFQ↓GP) (SEQ ID NO: 28). Enterokinase Factor Xa Additional protease cleavage sites include recognition sequences that are cleaved by a non- cytotoxic protease, for example by the light chain of a clostridial neurotoxin. These include the SNARE (e.g. SNAP-25, syntaxin, VAMP) protein recognition sequences that are cleaved by non-cytotoxic proteases such as the light chain of a clostridial neurotoxin. Clostridial neurotoxins comprising non-native protease cleavage sites are described in US 7,132,259, EP 1206554-B2 and US 2007/0166332, all of which are hereby incorporated by reference in their entirety. Also embraced by the term protease cleavage site is an intein, which is a self-cleaving sequence. The self-splicing reaction is controllable, for example by varying the concentration of reducing agent present. The present invention also embraces clostridial neurotoxins comprising a “destructive cleavage site”. In said clostridial neurotoxins, a non-native protease cleavage site is incorporated into the clostridial neurotoxin, at a location chosen such that cleavage at said site will decrease the activity of, or inactivate, the clostridial neurotoxin. The destructive protease cleavage site can be susceptible to cleavage by a local protease, in the event that the clostridial neurotoxin, following administration, migrates to a non-target location. Suitable non-native protease cleavage sites include those described above. Clostridial neurotoxins comprising a destructive cleavage site are described in WO 2010/094905 and WO 2002/044199, both of which are hereby incorporated by reference in their entirety. The modified clostridial neurotoxins of the present invention, especially the light chain component thereof, may be PEGylated – this may help to increase stability, for example duration of action of the light chain component. PEGylation is particularly preferred when the light chain comprises a BoNT/A, B or C1 protease. PEGylation preferably includes the addition of PEG to the N-terminus of the light chain component. By way of example, the N-terminus of a light chain may be extended with one or more amino acid (e.g. cysteine) residues, which may be the same or different. One or more of said amino acid residues may have its own PEG molecule attached (e.g. covalently attached) thereto. An example of this technology is described in WO2007/104567, which is hereby incorporated by reference in its entirety. The administration (e.g. dose) of a clostridial neurotoxin may be measured in nanograms.   Doses of clostridial neurotoxin according to the invention are to be understood as doses of active di-chain clostridial neurotoxin, i.e. without including the quantity of complexing proteins to which the neurotoxin may be associated with. In other words, it refers to the doses of active di-chain clostridial neurotoxin, whether said neurotoxin is administered to the patient in association to, or without, complexing proteins. As well-known to the skilled practitioner, an active di-chain clostridial neurotoxin is capable of binding to a membrane (e.g. cell membrane) receptor, translocating the light chain into the cytoplasm and of cleaving a SNARE protein, while complexing proteins do not display such biological activity (i.e. are not “active”). Additionally or alternatively, the doses of clostridial neurotoxin may be measured in “Units” (U) of clostridial neurotoxin. For example, the measurement of doses in Units may be particularly suitable when administering BoNT/A (or more particularly, for example, Dysport®). Indeed, as well known to the skilled practitioner, the potency of a clostridial neurotoxin is related to the quantity (e.g. nanograms) of neurotoxin required to achieve an LD50 (lethal dose 50) unit; one LD50 unit being defined as the median lethal intraperitoneal dose (as measured in mice). However, BoNT pharmaceutical preparations currently on the market contain different amount of 150 kD neurotoxin, but also of LD50 Units. Besides, in these preparations, the neurotoxin may, or may not, be associated with (i.e. combined with) non-toxic neurotoxin- associated proteins (NAP), also known as complexing proteins. For ease of conversion (as reported in Field et. al, “AbobotulinumtoxinA (Dysport®), OnabotulinumtoxinA (Botox®), and IncobotulinumtoxinA (Xeomin®) Neurotoxin Content and Potential Implications for Duration of Response in Patients”. Toxins 2018, 10(12), 535): - 100 Units of Botox® (also known as OnabotulinumtoxinA) contains about 0.9 ng of 150 kD BoNT/A, as well as complexing proteins; - 500 Units of Dysport® (also known as AbobotulinumtoxinA) contains about 2.69 ng of 150 kD BoNT/A, as well as complexing proteins; 1 Unit of Dysport® contains about 5.38 pg BoNT/A; - 100 Units of Xeomin® (also known as IncobotulinumtoxinA) contains about 0.40 ng of 150 kD BoNT/A, with no complexing proteins. It should be noted that conversion values may vary slightly. For example, conversion values reported in Frevert, 2012 (“Content of botulinum neurotoxin in Botox®/Vistabel®, Dysport®/Azzalure®, and Xeomin®/Bocouture®”; Drugs R D. 2010;10(2):67-73) are as follows:   - 100 Units of Botox® (also known as OnabotulinumtoxinA) contains about 0.73 ng of 150 kD BoNT/A, as well as complexing proteins; - 100 Units of Dysport® (also known as AbobotulinumtoxinA) contains about 0.65 ng of 150 kD BoNT/A, as well as complexing proteins; - 100 Units of Xeomin® (also known as IncobotulinumtoxinA) contains about 0.44 ng of 150 kD BoNT/A, with no complexing proteins; - 100 Units of Neurobloc/Myobloc® (also known as RimabotulinumtoxinB) contains about 0.2 ng to about 1 ng of 150 kD BoNT/B, as well as complexing proteins. The quantity of clostridial neurotoxin can be measured by the skilled practitioner according to methods conventionally used in the art to quantify proteins preferably at nanograms levels, including, among others, mass spectroscopy such as isotopic dilution mass spectroscopy (Muñoz et al., Quantification of protein calibrants by amino acid analysis using isotope dilution mass spectrometry, Anal. Biochem.2011, 408, 124–131), or fluorimetric assay (Poras et al., Detection and Quantification of Botulinum Neurotoxin Type A by a Novel Rapid In Vitro Fluorimetric Assay, Appl Environ Microbiol.2009 Jul; 75(13): 4382–4390). In one embodiment, a patient is administered at least 5000 Units, 6000 Units, 7000 Units, 8000 Units or 9000 Units, preferably at least 9500 Units, more preferably at least 9900 Units (e.g at least 10,000 Units) of a clostridial neurotoxin per 500 ml of solution. In one embodiment, a patient is administered less than or equal to 55,000 Units, 50,000 Units, 45,000 Units or 40,000 Units, preferably less than or equal to 35,000 Units, more preferably less than or equal to 31,000 Units (e.g. less than or equal to 30,000 Units) of a clostridial neurotoxin per 500 ml of solution. In one embodiment, a patient is administered 5000-35,000 Units, 6000-34,000 Units, 7000-33,000 Units, preferably 8000-32,000 Units, more preferably 9000-31,000 Units (e.g. preferably 10,000-30,000 Units) of a clostridial neurotoxin per 500 ml of solution. In one embodiment, a patient is administered at least 16,500 Units, 17,000 Units, 17,500 Units, 18,000 Units or 18,500 Units, preferably at least 19,000 Units, more preferably at least 19,500 Units (e.g. at least 20,000 Units) of a clostridial neurotoxin per 1 litre of solution. In one embodiment, a patient is administered less than or equal to 63,000 Units, 62,500 Units, 62,000 Units or 61,500 Units, preferably less than or equal to 61,000 Units, more preferably less than or equal to 60,500 Units (e.g. less than or equal to 60,000 Units) of a clostridial neurotoxin per 1 litre of solution. In one embodiment, a patient is administered 16,000-35,000 Units, 17,000- 34,000 Units, 18,000-33,000 Units, preferably 19,000-32,000 Units, more preferably 19,500-   60,500 Units (e.g. preferably 20,000-60,000 Units) of a clostridial neurotoxin per 1 litre of solution. In one embodiment, a patient is administered at least 51,000 pg, 51,500 pg, 52,000 pg or 52,500 pg, preferably at least 53,000 pg, more preferably at least 53,500 pg (e.g. at least 53,800 pg) of a clostridial neurotoxin per 500 ml of solution. In one embodiment, a patient is administered less than or equal to 164,000 pg 163,500 pg, 163,000 pg or 162,500 pg, preferably less than or equal to 162,000 pg, more preferably less than or equal to 161,700 pg (e.g. less than or equal to 161,400 pg) of a clostridial neurotoxin per 500 ml of solution. In one embodiment, a patient is administered 51,500-163,500 pg 52,000-163,000 pg or 52,500- 162,500 pg, preferably 53,000-162,000 pg, more preferably 53,500-161,700 pg (e.g.53,800- 161,400 pg) of a clostridial neurotoxin per 500 ml of solution. In one embodiment, a patient is administered at least 105,000 pg, 105,500 pg, 106,000 pg or 106,500 pg, preferably at least 107,000 pg, more preferably at least 107,400 pg (e.g. at least 107,600 pg) of a clostridial neurotoxin per 1 litre of solution. In one embodiment, a patient is administered less than or equal to 325,500 pg, 325,000 pg, 324,500 pg or 324,000 pg, preferably less than or equal to 323,500 pg, more preferably less than or equal to 323,000 pg (e.g. less than or equal to 322,800 pg) of a clostridial neurotoxin per 1 litre of solution. In one embodiment, a patient is administered 105,000-325,500 pg, 105,500-325,000 pg, 106,000- 324,500 pg or 106,500-324,000 pg, preferably 107,000-323,500 pg, more preferably 107,400- 323,000 pg (e.g.107,600-322,800 pg) of a clostridial neurotoxin per 1 litre of solution. In one embodiment, the solution comprises a clostridial neurotoxin and wherein the solution is physiologically inert and/or devoid of a denuding agent. In one embodiment, the solution comprises a clostridial neurotoxin and wherein the solution is saline based and/or devoid of a denuding agent. In one aspect the invention provides a pharmaceutical composition comprising the clostridial neurotoxin, and a pharmaceutically acceptable carrier, excipient, adjuvant, propellant and/or salt. In one aspect the invention provides kit of parts for use in a method of the invention, comprising: a) a solution consisting essentially of a clostridial neurotoxin; and b) a catheter for insertion into the bladder of the patient.   The terms “subject”, “individual” and “patient” may be used interchangeably herein to refer to a mammalian subject. In one embodiment the “subject” is a human, a companion animal (e.g. a pet such as a dog, cat, and/or rabbit), livestock (e.g. a pig, sheep, cattle, and/or a goat), and/or a horse. In a preferable embodiment, the subject (patient) is a human. The term “disorder” as used herein also encompasses a “disease”. In one embodiment the disorder is a disease. The term “treat” or “treating” as used herein encompasses prophylactic treatment (e.g. to prevent onset of a disorder) as well as corrective treatment (treatment of a subject already suffering from a disorder). Preferably “treat” or “treating” as used herein means corrective treatment. The term “treat” or “treating” as used herein refers to the disorder and/or a symptom thereof. Therefore, a polypeptide of the invention may be administered to a subject in a therapeutically effective amount or a prophylactically effective amount. Preferably a clostridial neurotoxin of the invention is administered to a subject in a therapeutically effective amount. A “therapeutically effective amount” is any amount of the clostridial neurotoxin, which when administered alone or in combination to a subject for treating said disorder (or a symptom thereof) is sufficient to effect such treatment of the disorder, or symptom thereof. A “prophylactically effective amount” is any amount of the clostridial neurotoxin that, when administered alone or in combination to a subject inhibits or delays the onset or reoccurrence of a disorder (or a symptom thereof). In some embodiments, the prophylactically effective amount prevents the onset or reoccurrence of a disorder entirely. “Inhibiting” the onset means either lessening the likelihood of a disorder’s onset (or symptom thereof), or preventing the onset entirely. SEQUENCE HOMOLOGY Any of a variety of sequence alignment methods can be used to determine percent identity, including, without limitation, global methods, local methods and hybrid methods, such as, e.g., segment approach methods. Protocols to determine percent identity are routine procedures within the scope of one skilled in the art. Global methods align sequences from the beginning to the end of the molecule and determine the best alignment by adding up scores of individual residue pairs and by imposing gap penalties. Non-limiting methods include, e.g., CLUSTAL W,   see, e.g., Julie D. Thompson et al., CLUSTAL W: Improving the Sensitivity of Progressive Multiple Sequence Alignment Through Sequence Weighting, Position- Specific Gap Penalties and Weight Matrix Choice, 22(22) Nucleic Acids Research 4673-4680 (1994); and iterative refinement, see, e.g., Osamu Gotoh, Significant Improvement in Accuracy of Multiple Protein. Sequence Alignments by Iterative Refinement as Assessed by Reference to Structural Alignments, 264(4) J. MoI. Biol.823-838 (1996). Local methods align sequences by identifying one or more conserved motifs shared by all of the input sequences. Non-limiting methods include, e.g., Match-box, see, e.g., Eric Depiereux and Ernest Feytmans, Match-Box: A Fundamentally New Algorithm for the Simultaneous Alignment of Several Protein Sequences, 8(5) CABIOS 501 -509 (1992); Gibbs sampling, see, e.g., C. E. Lawrence et al., Detecting Subtle Sequence Signals: A Gibbs Sampling Strategy for Multiple Alignment, 262(5131 ) Science 208-214 (1993); Align-M, see, e.g., Ivo Van WaIIe et al., Align-M - A New Algorithm for Multiple Alignment of Highly Divergent Sequences, 20(9) Bioinformatics:1428-1435 (2004). Thus, percent sequence identity is determined by conventional methods. See, for example, Altschul et al., Bull. Math. Bio.48: 603-16, 1986 and Henikoff and Henikoff, Proc. Natl. Acad. Sci. USA 89:10915-19, 1992. Briefly, two amino acid sequences are aligned to optimize the alignment scores using a gap opening penalty of 10, a gap extension penalty of 1, and the "blosum 62" scoring matrix of Henikoff and Henikoff (ibid.) as shown below (amino acids are indicated by the standard one-letter codes). The "percent sequence identity" between two or more nucleic acid or amino acid sequences is a function of the number of identical positions shared by the sequences. Thus, % identity may be calculated as the number of identical nucleotides / amino acids divided by the total number of nucleotides / amino acids, multiplied by 100. Calculations of % sequence identity may also take into account the number of gaps, and the length of each gap that needs to be introduced to optimize alignment of two or more sequences. Sequence comparisons and the determination of percent identity between two or more sequences can be carried out using specific mathematical algorithms, such as BLAST, which will be familiar to a skilled person.   IDENTITY A 4 R -1 5 N -2 0 6 D -2 -2 1 6 C 0 -3 -3 -3 9 Q -1 1 0 0 -3 5 E -1 0 0 2 -4 2 5 G 0 -2 0 -1 -3 -2 -2 6 H -2 0 1 -1 -3 0 0 -2 8 I -1 -3 -3 -3 -1 -3 -3 -4 -3 4 L -1 -2 -3 -4 -1 -2 -3 -4 -3 2 4 K -1 2 0 -1 -3 1 1 -2 -1 -3 -2 5 M -1 -1 -2 -3 -1 0 -2 -3 -2 1 2 -1 5 F -2 -3 -3 -3 -2 -3 -3 -3 -1 0 0 -3 0 6 P -1 -2 -2 -1 -3 -1 -1 -2 -2 -3 -3 -1 -2 -4 7 S 1 -1 1 0 -1 0 0 0 -1 -2 -2 0 -1 -2 -1 4 T 0 -1 0 -1 -1 -1 -1 -2 -2 -1 -1 -1 -1 -2 -1 1 5 W -3 -3 -4 -4 -2 -2 -3 -2 -2 -3 -2 -3 -1 1 -4 -3 -211 Y -2 -2 -2 -3 -2 -1 -2 -3 2 -1 -1 -2 -1 3 -3 -2 -2 2 7 V 0 -3 -3 -3 -1 -2 -2 -3 -3 3 1 -2 1 -1 -2 -2 0 -3 -1 4 The percent identity is then calculated as: Total number of identical matches __________________________________________ x 100 [length of the longer sequence plus the number of gaps introduced into the longer sequence in order to align the two sequences] Substantially homologous polypeptides are characterized as having one or more amino acid substitutions, deletions or additions. These changes are preferably of a minor nature, that is conservative amino acid substitutions (see below) and other substitutions that do not significantly affect the folding or activity of the polypeptide; small deletions, typically of one to about 30 amino acids; and small amino- or carboxyl-terminal extensions, such as an amino-   terminal methionine residue, a small linker peptide of up to about 20-25 residues, or an affinity tag. CONSERVATIVE AMINO ACID SUBSTITUTIONS Basic: arginine lysine histidine Acidic: glutamic acid aspartic acid Polar: glutamine asparagine Hydrophobic: leucine isoleucine valine Aromatic: phenylalanine tryptophan tyrosine Small: glycine alanine serine threonine methionine In addition to the 20 standard amino acids, non-standard amino acids (such as 4- hydroxyproline, 6-N-methyl lysine, 2-aminoisobutyric acid, isovaline and α -methyl serine) may be substituted for amino acid residues of the polypeptides of the present invention. A limited number of non-conservative amino acids, amino acids that are not encoded by the genetic code, and unnatural amino acids may be substituted for polypeptide amino acid residues. The polypeptides of the present invention can also comprise non-naturally occurring amino acid residues. Non-naturally occurring amino acids include, without limitation, trans-3-methylproline, 2,4- methano-proline, cis-4-hydroxyproline, trans-4-hydroxy-proline, N-methylglycine, allo- threonine, methyl-threonine, hydroxy-ethylcysteine, hydroxyethylhomo-cysteine, nitro- glutamine, homoglutamine, pipecolic acid, tert-leucine, norvaline, 2-azaphenylalanine, 3- azaphenyl-alanine, 4-azaphenyl-alanine, and 4-fluorophenylalanine. Several methods are   known in the art for incorporating non-naturally occurring amino acid residues into proteins. For example, an in vitro system can be employed wherein nonsense mutations are suppressed using chemically aminoacylated suppressor tRNAs. Methods for synthesizing amino acids and aminoacylating tRNA are known in the art. Transcription and translation of plasmids containing nonsense mutations is carried out in a cell free system comprising an E. coli S30 extract and commercially available enzymes and other reagents. Proteins are purified by chromatography. See, for example, Robertson et al., J. Am. Chem. Soc.113:2722, 1991; Ellman et al., Methods Enzymol.202:301, 1991; Chung et al., Science 259:806-9, 1993; and Chung et al., Proc. Natl. Acad. Sci. USA 90:10145-9, 1993). In a second method, translation is carried out in Xenopus oocytes by microinjection of mutated mRNA and chemically aminoacylated suppressor tRNAs (Turcatti et al., J. Biol. Chem. 271:19991-8, 1996). Within a third method, E. coli cells are cultured in the absence of a natural amino acid that is to be replaced (e.g., phenylalanine) and in the presence of the desired non-naturally occurring amino acid(s) (e.g., 2-azaphenylalanine, 3-azaphenylalanine, 4-azaphenylalanine, or 4-fluorophenylalanine). The non-naturally occurring amino acid is incorporated into the polypeptide in place of its natural counterpart. See, Koide et al., Biochem.33:7470-6, 1994. Naturally occurring amino acid residues can be converted to non-naturally occurring species by in vitro chemical modification. Chemical modification can be combined with site-directed mutagenesis to further expand the range of substitutions (Wynn and Richards, Protein Sci.2:395-403, 1993). A limited number of non-conservative amino acids, amino acids that are not encoded by the genetic code, non-naturally occurring amino acids, and unnatural amino acids may be substituted for amino acid residues of polypeptides of the present invention. Essential amino acids in the polypeptides of the present invention can be identified according to procedures known in the art, such as site-directed mutagenesis or alanine-scanning mutagenesis (Cunningham and Wells, Science 244: 1081-5, 1989). Sites of biological interaction can also be determined by physical analysis of structure, as determined by such techniques as nuclear magnetic resonance, crystallography, electron diffraction or photoaffinity labeling, in conjunction with mutation of putative contact site amino acids. See, for example, de Vos et al., Science 255:306-12, 1992; Smith et al., J. Mol. Biol. 224:899-904, 1992; Wlodaver et al., FEBS Lett.309:59-64, 1992. The identities of essential amino acids can also be inferred from analysis of homologies with related components (e.g. the translocation or protease components) of the polypeptides of the present invention.   Multiple amino acid substitutions can be made and tested using known methods of mutagenesis and screening, such as those disclosed by Reidhaar-Olson and Sauer (Science 241:53-7, 1988) or Bowie and Sauer (Proc. Natl. Acad. Sci. USA 86:2152-6, 1989). Briefly, these authors disclose methods for simultaneously randomizing two or more positions in a polypeptide, selecting for functional polypeptide, and then sequencing the mutagenized polypeptides to determine the spectrum of allowable substitutions at each position. Other methods that can be used include phage display (e.g., Lowman et al., Biochem.30:10832-7, 1991; Ladner et al., U.S. Patent No.5,223,409; Huse, WIPO Publication WO 92/06204) and region-directed mutagenesis (Derbyshire et al., Gene 46:145, 1986; Ner et al., DNA 7:127, 1988). Multiple amino acid substitutions can be made and tested using known methods of mutagenesis and screening, such as those disclosed by Reidhaar-Olson and Sauer (Science 241:53-7, 1988) or Bowie and Sauer (Proc. Natl. Acad. Sci. USA 86:2152-6, 1989). Briefly, these authors disclose methods for simultaneously randomizing two or more positions in a polypeptide, selecting for functional polypeptide, and then sequencing the mutagenized polypeptides to determine the spectrum of allowable substitutions at each position. Other methods that can be used include phage display (e.g., Lowman et al., Biochem.30:10832-7, 1991; Ladner et al., U.S. Patent No.5,223,409; Huse, WIPO Publication WO 92/06204) and region-directed mutagenesis (Derbyshire et al., Gene 46:145, 1986; Ner et al., DNA 7:127, 1988). Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Singleton, et al., DICTIONARY OF MICROBIOLOGY AND MOLECULAR BIOLOGY, 20 ED., John Wiley and Sons, New York (1994), and Hale & Marham, THE HARPER COLLINS DICTIONARY OF BIOLOGY, Harper Perennial, NY (1991) provide the skilled person with a general dictionary of many of the terms used in this disclosure. This disclosure is not limited by the exemplary methods and materials disclosed herein, and any methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of this disclosure. Numeric ranges are inclusive of the numbers defining the range. Unless otherwise indicated, any nucleic acid sequences are written left to right in 5' to 3' orientation; amino acid sequences are written left to right in amino to carboxy orientation, respectively.   The headings provided herein are not limitations of the various aspects or embodiments of this disclosure. Amino acids are referred to herein using the name of the amino acid, the three letter abbreviation or the single letter abbreviation. The term “protein", as used herein, includes proteins, polypeptides, and peptides. As used herein, the term “amino acid sequence” is synonymous with the term “polypeptide” and/or the term “protein”. In some instances, the term “amino acid sequence” is synonymous with the term “peptide”. In some instances, the term “amino acid sequence” is synonymous with the term “enzyme”. The terms "protein" and "polypeptide" are used interchangeably herein. In the present disclosure and claims, the conventional one-letter and three-letter codes for amino acid residues may be used. The 3- letter code for amino acids as defined in conformity with the IUPACIUB Joint Commission on Biochemical Nomenclature (JCBN). It is also understood that a polypeptide may be coded for by more than one nucleotide sequence due to the degeneracy of the genetic code. Other definitions of terms may appear throughout the specification. Before the exemplary embodiments are described in more detail, it is to be understood that this disclosure is not limited to particular embodiments described, and as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be defined only by the appended claims. Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within this disclosure. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within this disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in this disclosure. It must be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a clostridial neurotoxin” includes a plurality of such candidate agents   and reference to “the clostridial neurotoxin” includes reference to one or more clostridial neurotoxins and equivalents thereof known to those skilled in the art, and so forth. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that such publications constitute prior art to the claims appended hereto. BRIEF DESCRIPTION OF THE DRAWINGS Embodiments of the invention will now be described, by way of example only, with reference to the following Figures and Examples. Figure 1 shows a schematic of a procedure that involves intradetrusor injections. This procedure involves the careful manipulation of a device through the opening and along the length of the urethra, and into the bladder of a patient. Cytoscopic guidance then allows sequential manoeuvring of a needle to multiple, predetermined injection sites located across the bladder wall lining. Each injection involves penetration of the needle through the bladder wall lining and results in the delivery of a metred dose of therapeutic agent at each injection site. Figure 2 shows a schematic of the light pressure filling approach. A catheter is inserted into a patient’s urethra and any urine present in the bladder is drained. A small volume (e.g.50 ml) of medication is then slowly filled through the catheter and into the bladder. The catheter is removed and the patient instructed to resume normal daily activities though not to empty their bladder for at least 15 minutes, preferably at least 90 minutes. In doing so, the medication is allowed to contact and potentially treat the whole bladder wall lining. Figure 3 is a schematic showing the administration of BoNT/A via intradetrusor injections. Intradetrusor injections of BoNT/A are highly invasive and simultaneously target all three levels of innervation of the bladder wall, namely: the urothelium; the afferent terminals of the lamina propria; and the efferent terminals of the detrusor muscle. Figure 4 is a schematic showing the method of the present invention. The method of the present invention is less invasive and targets the urothelium and the afferent terminals of the lamina propria.   Figure 5 shows the study design for assessing the effects of Dysport in a chronic rat model of interstitial cystitis/bladder pain syndrome (CYP-induced interstitial cystitis/bladder pain syndrome). Figure 6 shows the effects (based on nociceptive scores) of Dysport (10, 20 and 30 U/rat, i.ves.) on CYP-induced chronic visceral pain. Nociceptive scores in %, at D10 (A) and D12 (B) in Dysport- and Vehicle-treated rats. Results are expressed as mean ± s.e.m. Grouped comparison Two-way RM ANOVA with Sidak’s post test vs CYP/Vehicle (### p<0.001). Figure 7 shows the effects (based on nociceptive threshold) of test and reference substances on CYP-induced chronic allodynia. Nociceptive threshold in g, before (“D0”) and once saline or CYP was injected but before initiation of the pharmacological treatment (“D7”) (A) and at D10 (B) and D12 (C) in the Dysport, DMSO, Ialuril and Vehicle groups. Results are expressed as mean ± s.e.m. No statistical analysis was performed. Figure 8 shows the effects (based on AUC 1- 6 g) of test and reference substances on CYP- induced chronic allodynia. AUC calculated between 1 and 6 g, before (“D0”) and once saline or CYP was injected but before initiation of the pharmacological treatment (“D7”) (A) and at D10 (B) and D12 (C) in the Dysport, DMSO, Ialuril and Vehicle groups. Results are expressed as mean ± s.e.m. No statistical analysis was performed. Figure 9 shows the effects (based on AUC 6-26 g) of test and reference substances on CYP- induced chronic hyperalgesia. AUC calculated between 6 and 26 g, before (“D0”) and once saline or CYP was injected but before initiation of the pharmacological treatment (“D7”) (A) and at D10 (B) and D12 (C) in the Dysport, DMSO, Ialuril and Vehicle groups. Results are expressed as mean ± s.e.m. No statistical analysis was performed. Figure 10 is a schematic diagram showing the setup of the ex vivo bladder electrophysiology preparation. The bladder was catheterised at the urethra and through the dome. The pelvic nerve (PN) and hypogastric nerve (HGN) bundles were inserted to a glass recording electrode. The technical setup on the right visualises how the input from the pressure transducer and the electrode is modified by the hardware and the Spike2 software to give the example distension image at the top. Figure created using BioRender. Figure 11 shows that intravesical BoNT/A treatment led to significant decreases in bladder mechanosensitivity and increases in the pressure-volume relationship. A) Afferent responses   to distension were significantly reduced 30, 60 and 90 minutes after treatment (p<0.0001, n = 9, two-way ANOVA). B) The pressure-volume relationship was significantly increased after intravesical Dysport compared to control (p = 0.0003; n = 9; two-way ANOVA). Figure 12 shows the effect of BoNT/B on bladder mechanosensitivity. A) Afferent responses to distension were reduced in a time dependent manner following BoNT/B treatment (p<0.0001; n = 6; two-way ANOVA). B) the pressure-volume relationship was significantly higher following BoNT/B treatment (p <0.0001; two-way ANOVA). Figure 13 shows the effect of BoNT/E on bladder mechanosensitivity. A) Afferent responses to distension were significantly reduced in a time dependent manner following BoNT/E treatment (p<0.0001; n = 5; two-way ANOVA). B) the pressure-volume relationship was significantly higher following BoNT/E treatment (p <0.0001; two-way ANOVA). SEQUENCE LISTING Where an initial Met amino acid residue or a corresponding initial codon is indicated in any of the following SEQ ID NOs, said residue/codon is optional.   SEQ ID NO: 1 - Nucleotide Sequence of Unmodified BoNT/A ATGCCATTCGTCAACAAGCAATTCAACTACAAAGACCCAGTCAACGGCGTCGACATCGCA TACATCAAGATTCCGAACGCCGG TCAAATGCAGCCGGTTAAGGCTTTTAAGATCCACAACAAGATTTGGGTTATCCCGGAGCG TGACACCTTCACGAACCCGGAAG AAGGCGATCTGAACCCGCCACCGGAAGCGAAGCAAGTCCCTGTCAGCTACTACGATTCGA CGTACCTGAGCACGGATAACGAA AAAGATAACTACCTGAAAGGTGTGACCAAGCTGTTCGAACGTATCTACAGCACGGATCTG GGTCGCATGCTGCTGACTAGCAT TGTTCGCGGTATCCCGTTCTGGGGTGGTAGCACGATTGACACCGAACTGAAGGTTATCGA CACTAACTGCATTAACGTTATTC AACCGGATGGTAGCTATCGTAGCGAAGAGCTGAATCTGGTCATCATTGGCCCGAGCGCAG ACATTATCCAATTCGAGTGCAAG AGCTTTGGTCACGAGGTTCTGAATCTGACCCGCAATGGCTATGGTAGCACCCAGTACATT CGTTTTTCGCCGGATTTTACCTT CGGCTTTGAAGAGAGCCTGGAGGTTGATACCAATCCGTTGCTGGGTGCGGGCAAATTCGC TACCGATCCGGCTGTCACGCTGG CCCATGAACTGATCCACGCAGGCCACCGCCTGTACGGCATTGCCATCAACCCAAACCGTG TGTTCAAGGTTAATACGAATGCA TACTACGAGATGAGCGGCCTGGAAGTCAGCTTCGAAGAACTGCGCACCTTCGGTGGCCAT GACGCTAAATTCATTGACAGCTT GCAAGAGAATGAGTTCCGTCTGTACTACTATAACAAATTCAAAGACATTGCAAGCACGTT GAACAAGGCCAAAAGCATCGTTG GTACTACCGCGTCGTTGCAGTATATGAAGAATGTGTTTAAAGAGAAGTACCTGCTGTCCG AGGATACCTCCGGCAAGTTTAGC GTTGATAAGCTGAAGTTTGACAAACTGTACAAGATGCTGACCGAGATTTACACCGAGGAC AACTTTGTGAAATTCTTCAAAGT GTTGAATCGTAAAACCTATCTGAATTTTGACAAAGCGGTTTTCAAGATTAACATCGTGCC GAAGGTGAACTACACCATCTATG ACGGTTTTAACCTGCGTAACACCAACCTGGCGGCGAACTTTAACGGTCAGAATACGGAAA TCAACAACATGAATTTCACGAAG TTGAAGAACTTCACGGGTCTGTTCGAGTTCTATAAGCTGCTGTGCGTGCGCGGTATCATC ACCAGCAAAACCAAAAGCCTGGA CAAAGGCTACAACAAGGCGCTGAATGACCTGTGCATTAAGGTAAACAATTGGGATCTGTT CTTTTCGCCATCCGAAGATAATT TTACCAACGACCTGAACAAGGGTGAAGAAATCACCAGCGATACGAATATTGAAGCAGCGG AAGAGAATATCAGCCTGGATCTG ATCCAGCAGTACTATCTGACCTTTAACTTCGACAATGAACCGGAGAACATTAGCATTGAG AATCTGAGCAGCGACATTATCGG TCAGCTGGAACTGATGCCGAATATCGAACGTTTCCCGAACGGCAAAAAGTACGAGCTGGA CAAGTACACTATGTTCCATTACC TGCGTGCACAGGAGTTTGAACACGGTAAAAGCCGTATCGCGCTGACCAACAGCGTTAACG AGGCCCTGCTGAACCCGAGCCGT GTCTATACCTTCTTCAGCAGCGACTATGTTAAGAAAGTGAACAAAGCCACTGAGGCCGCG ATGTTCCTGGGCTGGGTGGAACA GCTGGTATATGACTTCACGGACGAGACGAGCGAAGTGAGCACTACCGACAAAATTGCTGA TATTACCATCATTATCCCGTATA TTGGTCCGGCACTGAACATTGGCAACATGCTGTACAAAGACGATTTTGTGGGTGCCCTGA TCTTCTCCGGTGCCGTGATTCTG CTGGAGTTCATTCCGGAGATTGCGATCCCGGTGTTGGGTACCTTCGCGCTGGTGTCCTAC ATCGCGAATAAGGTTCTGACGGT TCAGACCATCGATAACGCGCTGTCGAAACGTAATGAAAAATGGGACGAGGTTTACAAATA CATTGTTACGAATTGGCTGGCGA AAGTCAATACCCAGATCGACCTGATCCGTAAGAAAATGAAAGAGGCGCTGGAGAATCAGG CGGAGGCCACCAAAGCAATTATC AACTACCAATACAACCAGTACACGGAAGAAGAGAAGAATAACATTAACTTCAATATCGAT GATTTGAGCAGCAAGCTGAATGA ATCTATCAACAAAGCGATGATCAATATCAACAAGTTTTTGAATCAGTGTAGCGTTTCGTA CCTGATGAATAGCATGATTCCGT ATGGCGTCAAACGTCTGGAGGACTTCGACGCCAGCCTGAAAGATGCGTTGCTGAAATACA TTTACGACAATCGTGGTACGCTG ATTGGCCAAGTTGACCGCTTGAAAGACAAAGTTAACAATACCCTGAGCACCGACATCCCA TTTCAACTGAGCAAGTATGTTGA TAATCAACGTCTGTTGAGCACTTTCACCGAGTATATCAAAAACATCATCAATACTAGCAT TCTGAACCTGCGTTACGAGAGCA ATCATCTGATTGATCTGAGCCGTTATGCAAGCAAGATCAACATCGGTAGCAAGGTCAATT TTGACCCGATCGATAAGAACCAG   ATCCAGCTGTTTAATCTGGAATCGAGCAAAATTGAGGTTATCCTGAAAAACGCCATTGTC TACAACTCCATGTACGAGAATTT CTCCACCAGCTTCTGGATTCGCATCCCGAAATACTTCAACAGCATTAGCCTGAACAACGA GTATACTATCATCAACTGTATGG AGAACAACAGCGGTTGGAAGGTGTCTCTGAACTATGGTGAGATCATTTGGACCTTGCAGG ACACCCAAGAGATCAAGCAGCGC GTCGTGTTCAAGTACTCTCAAATGATCAACATTTCCGATTACATTAATCGTTGGATCTTC GTGACCATTACGAATAACCGTCT GAATAACAGCAAGATTTACATCAATGGTCGCTTGATCGATCAGAAACCGATTAGCAACCT GGGTAATATCCACGCAAGCAACA ACATTATGTTCAAATTGGACGGTTGCCGCGATACCCATCGTTATATCTGGATCAAGTATT TCAACCTGTTTGATAAAGAACTG AATGAGAAGGAGATCAAAGATTTGTATGACAACCAATCTAACAGCGGCATTTTGAAGGAC TTCTGGGGCGATTATCTGCAATA CGATAAGCCGTACTATATGCTGAACCTGTATGATCCGAACAAATATGTGGATGTCAATAA TGTGGGTATTCGTGGTTACATGT ATTTGAAGGGTCCGCGTGGCAGCGTTATGACGACCAACATTTACCTGAACTCTAGCCTGT ACCGTGGTACGAAATTCATCATT AAGAAATATGCCAGCGGCAACAAAGATAACATTGTGCGTAATAACGATCGTGTCTACATC AACGTGGTCGTGAAGAATAAAGA GTACCGTCTGGCGACCAACGCTTCGCAGGCGGGTGTTGAGAAAATTCTGAGCGCGTTGGA GATCCCTGATGTCGGTAATCTGA GCCAAGTCGTGGTTATGAAGAGCAAGAACGACCAGGGTATCACTAACAAGTGCAAGATGA ACCTGCAAGACAACAATGGTAAC GACATCGGCTTTATTGGTTTCCACCAGTTCAACAATATTGCTAAACTGGTAGCGAGCAAT TGGTACAATCGTCAGATTGAGCG CAGCAGCCGTACTTTGGGCTGTAGCTGGGAGTTTATCCCGGTCGATGATGGTTGGGGCGA ACGTCCGCTG SEQ ID NO: 2 - Polypeptide Sequence of Unmodified BoNT/A MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN PPPEAKQVPVSYYDSTYLSTDNE KDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGS YRSEELNLVIIGPSADIIQFECK SFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELI HAGHRLYGIAINPNRVFKVNTNA YYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTAS LQYMKNVFKEKYLLSEDTSGKFS VDKLKFDKLYKMLTEIYTEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNL RNTNLAANFNGQNTEINNMNFTK LKNFTGLFEFYKLLCVRGIITSKTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDL NKGEEITSDTNIEAAEENISLDL IQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNGKKYELDKYTMFHYLRAQE FEHGKSRIALTNSVNEALLNPSR VYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPAL NIGNMLYKDDFVGALIFSGAVIL LEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQ IDLIRKKMKEALENQAEATKAII NYQYNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIPYGVKR LEDFDASLKDALLKYIYDNRGTL IGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKNIINTSILNLRYESNHLID LSRYASKINIGSKVNFDPIDKNQ IQLFNLESSKIEVILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNNEYTIINCMENNSG WKVSLNYGEIIWTLQDTQEIKQR VVFKYSQMINISDYINRWIFVTITNNRLNNSKIYINGRLIDQKPISNLGNIHASNNIMFK LDGCRDTHRYIWIKYFNLFDKEL NEKEIKDLYDNQSNSGILKDFWGDYLQYDKPYYMLNLYDPNKYVDVNNVGIRGYMYLKGP RGSVMTTNIYLNSSLYRGTKFII KKYASGNKDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVV MKSKNDQGITNKCKMNLQDNNGN DIGFIGFHQFNNIAKLVASNWYNRQIERSSRTLGCSWEFIPVDDGWGERPL   SEQ ID NO: 3 - BoNT/B1, accession number B1INP5, amino acid sequence MPVTINNFNYNDPIDNNNIIMMEPPFARGTGRYYKAFKITDRIWIIPERYTFGYKPEDFN KSSGIFNRDVCEYYDPDYLN TNDKKNIFLQTMIKLFNRIKSKPLGEKLLEMIINGIPYLGDRRVPLEEFNTNIASVTVNK LISNPGEVERKKGIFANLII FGPGPVLNENETIDIGIQNHFASREGFGGIMQMKFCPEYVSVFNNVQENKGASIFNRRGY FSDPALILMHELIHVLHGLY GIKVDDLPIVPNEKKFFMQSTDAIQAEELYTFGGQDPSIITPSTDKSIYDKVLQNFRGIV DRLNKVLVCISDPNININIY KNKFKDKYKFVEDSEGKYSIDVESFDKLYKSLMFGFTETNIAENYKIKTRASYFSDSLPP VKIKNLLDNEIYTIEEGFNI SDKDMEKEYRGQNKAINKQAYEEISKEHLAVYKIQMCKSVKAPGICIDVDNEDLFFIADK NSFSDDLSKNERIEYNTQSN YIENDFPINELILDTDLISKIELPSENTESLTDFNVDVPVYEKQPAIKKIFTDENTIFQY LYSQTFPLDIRDISLTSSFD DALLFSNKVYSFFSMDYIKTANKVVEAGLFAGWVKQIVNDFVIEANKSNTMDKIADISLI VPYIGLALNVGNETAKGNFE NAFEIAGASILLEFIPELLIPVVGAFLLESYIDNKNKIIKTIDNALTKRNEKWSDMYGLI VAQWLSTVNTQFYTIKEGMY KALNYQAQALEEIIKYRYNIYSEKEKSNINIDFNDINSKLNEGINQAIDNINNFINGCSV SYLMKKMIPLAVEKLLDFDN TLKKNLLNYIDENKLYLIGSAEYEKSKVNKYLKTIMPFDLSIYTNDTILIEMFNKYNSEI LNNIILNLRYKDNNLIDLSG YGAKVEVYDGVELNDKNQFKLTSSANSKIRVTQNQNIIFNSVFLDFSVSFWIRIPKYKND GIQNYIHNEYTIINCMKNNS GWKISIRGNRIIWTLIDINGKTKSVFFEYNIREDISEYINRWFFVTITNNLNNAKIYING KLESNTDIKDIREVIANGEI IFKLDGDIDRTQFIWMKYFSIFNTELSQSNIEERYKIQSYSEYLKDFWGNPLMYNKEYYM FNAGNKNSYIKLKKDSPVGE ILTRSKYNQNSKYINYRDLYIGEKFIIRRKSNSQSINDDIVRKEDYIYLDFFNLNQEWRV YTYKYFKKEEEKLFLAPISD SDEFYNTIQIKEYDEQPTYSCQLLFKKDEESTDEIGLIGIHRFYESGIVFEEYKDYFCIS KWYLKEVKRKPYNLKLGCNW QFIPKDEGWTE     SEQ ID NO: 4 - BoNT/C1, accession number P18640, amino acid sequence MPITINNFNYSDPVDNKNILYLDTHLNTLANEPEKAFRITGNIWVIPDRFSRNSNPNLNK PPRVTSPKSGYYDPNYLSTD SDKDPFLKEIIKLFKRINSREIGEELIYRLSTDIPFPGNNNTPINTFDFDVDFNSVDVKT RQGNNWVKTGSINPSVIITG PRENIIDPETSTFKLTNNTFAAQEGFGALSIISISPRFMLTYSNATNDVGEGRFSKSEFC MDPILILMHELNHAMHNLYG IAIPNDQTISSVTSNIFYSQYNVKLEYAEIYAFGGPTIDLIPKSARKYFEEKALDYYRSI AKRLNSITTANPSSFNKYIG EYKQKLIRKYRFVVESSGEVTVNRNKFVELYNELTQIFTEFNYAKIYNVQNRKIYLSNVY TPVTANILDDNVYDIQNGFN IPKSNLNVLFMGQNLSRNPALRKVNPENMLYLFTKFCHKAIDGRSLYNKTLDCRELLVKN TDLPFIGDISDVKTDIFLRK DINEETEVIYYPDNVSVDQVILSKNTSEHGQLDLLYPSIDSESEILPGENQVFYDNRTQN VDYLNSYYYLESQKLSDNVE DFTFTRSIEEALDNSAKVYTYFPTLANKVNAGVQGGLFLMWANDVVEDFTTNILRKDTLD KISDVSAIIPYIGPALNISN SVRRGNFTEAFAVTGVTILLEAFPEFTIPALGAFVIYSKVQERNEIIKTIDNCLEQRIKR WKDSYEWMMGTWLSRIITQF NNISYQMYDSLNYQAGAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNIN KFIRECSVTYLFKNMLPKVI DELNEFDRNTKAKLINLIDSHNIILVGEVDKLKAKVNNSFQNTIPFNIFSYTNNSLLKDI INEYFNNINDSKILSLQNRK NTLVDTSGYNAEVSEEGDVQLNPIFPFDFKLGSSGEDRGKVIVTQNENIVYNSMYESFSI SFWIRINKWVSNLPGYTIID SVKNNSGWSIGIISNFLVFTLKQNEDSEQSINFSYDISNNAPGYNKWFFVTVTNNMMGNM KIYINGKLIDTIKVKELTGI NFSKTITFEINKIPDTGLITSDSDNINMWIRDFYIFAKELDGKDINILFNSLQYTNVVKD YWGNDLRYNKEYYMVNIDYL NRYMYANSRQIVFNTRRNNNDFNEGYKIIIKRIRGNTNDTRVRGGDILYFDMTINNKAYN LFMKNETMYADNHSTEDIYA IGLREQTKDINDNIIFQIQPMNNTYYYASQIFKSNFNGENISGICSIGTYRFRLGGDWYR HNYLVPTVKQGNYASLLEST STHWGFVPVSE   SEQ ID NO: 5 - BoNT/D, accession number P19321, amino acid sequence MTWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSK PPRPTSKYQSYYDPSYLSTD EQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEK FENGSWKVTNIITPSVLIFG PLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFC MDPVIALMHELTHSLHQLYG INIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDI AKRLNNINKTIPSSWISNID KYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHY LPVFANILDDNIYTIRDGFN LTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCLRLTKNSRDDSTCIKVKNNRLPY VADKDSISQEIFENKIITDE TNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYL NSYYYLESQKLSNNVENITL TTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISD VSVIIPYIGPALNIGNSALR GNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDS YQWMVSNWLSRITTQFNHIN YQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIR ECSVTYLFKNMLPKVIDELN KFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEY FNSINDSKILSLQNKKNALV DTSGYNAEVRVGDNVQLNTIYTNDFKLSSSGDKIIVNLNNNILYSAIYENSSVSFWIKIS KDLTNSHNEYTIINSIEQNS GWKLCIRNGNIEWILQDVNRKYKSLIFDYSESLSHTGYTNKWFFVTITNNIMGYMKLYIN GELKQSQKIEDLDEVKLDKT IVFGIDENIDENQMLWIRDFNIFSKELSNEDINIVYEGQILRNVIKDYWGNPLKFDTEYY IINDNYIDRYIAPESNVLVL VQYPDRSKLYTGNPITIKSVSDKNPYSRILNGDNIILHMLYNSRKYMIIRDTDTIYATQG GECSQNCVYALKLQSNLGNY GIGIFSIKNIVSKNKYCSQIFSSFRENTMLLADIYKPWRFSFKNAYTPVAVTNYETKLLS TSSFWKFISRDPGWVE   SEQ ID NO: 6 - BoNT/E1, accession number WP_003372387, amino acid sequence MPKINSFNYNDPVNDRTILYIKPGGCQEFYKSFNIMKNIWIIPERNVIGTTPQDFHPPTS LKNGDSSYYDPNYLQSDEEK DRFLKIVTKIFNRINNNLSGGILLEELSKANPYLGNDNTPDNQFHIGDASAVEIKFSNGS QDILLPNVIIMGAEPDLFET NSSNISLRNNYMPSNHGFGSIAIVTFSPEYSFRFNDNSMNEFIQDPALTLMHELIHSLHG LYGAKGITTKYTITQKQNPL ITNIRGTNIEEFLTFGGTDLNIITSAQSNDIYTNLLADYKKIASKLSKVQVSNPLLNPYK DVFEAKYGLDKDASGIYSVN INKFNDIFKKLYSFTEFDLATKFQVKCRQTYIGQYKYFKLSNLLNDSIYNISEGYNINNL KVNFRGQNANLNPRIITPIT GRGLVKKIIRFCKNIVSVKGIRKSICIEINNGELFFVASENSYNDDNINTPKEIDDTVTS NNNYENDLDQVILNFNSESA PGLSDEKLNLTIQNDAYIPKYDSNGTSDIEQHDVNELNVFFYLDAQKVPEGENNVNLTSS IDTALLEQPKIYTFFSSEFI NNVNKPVQAALFVSWIQQVLVDFTTEANQKSTVDKIADISIVVPYIGLALNIGNEAQKGN FKDALELLGAGILLEFEPEL LIPTILVFTIKSFLGSSDNKNKVIKAINNALKERDEKWKEVYSFIVSNWMTKINTQFNKR KEQMYQALQNQVNAIKTIIE SKYNSYTLEEKNELTNKYDIKQIENELNQKVSIAMNNIDRFLTESSISYLMKLINEVKIN KLREYDENVKTYLLNYIIQH GSILGESQQELNSMVTDTLNNSIPFKLSSYTDDKILISYFNKFFKRIKSSSVLNMRYKND KYVDTSGYDSNININGDVYK YPTNKNQFGIYNDKLSEVNISQNDYIIYDNKYKNFSISFWVRIPNYDNKIVNVNNEYTII NCMRDNNSGWKVSLNHNEII WTLQDNAGINQKLAFNYGNANGISDYINKWIFVTITNDRLGDSKLYINGNLIDQKSILNL GNIHVSDNILFKIVNCSYTR YIGIRYFNIFDKELDETEIQTLYSNEPNTNILKDFWGNYLLYDKEYYLLNVLKPNNFIDR RKDSTLSINNIRSTILLANR LYSGIKVKIQRVNNSSTNDNLVRKNDQVYINFVASKTHLFPLYADTATTNKEKTIKISSS GNRFNQVVVMNSVGNNCTMN FKNNNGNNIGLLGFKADTVVASTWYYTHMRDHTNSNGCFWNFISEEHGWQEK   SEQ ID NO: 7 - BoNT/F1, accession number Q57236, amino acid MPVVINSFNYNDPVNDDTILYMQIPYEEKSKKYYKAFEIMRNVWIIPERNTIGTDPSDFD PPASLENGSSAYYDPNYLTT DAEKDRYLKTTIKLFKRINSNPAGEVLLQEISYAKPYLGNEHTPINEFHPVTRTTSVNIK SSTNVKSSIILNLLVLGAGP DIFENSSYPVRKLMDSGGVYDPSNDGFGSINIVTFSPEYEYTFNDISGGYNSSTESFIAD PAISLAHELIHALHGLYGAR GVTYKETIKVKQAPLMIAEKPIRLEEFLTFGGQDLNIITSAMKEKIYNNLLANYEKIATR LSRVNSAPPEYDINEYKDYF QWKYGLDKNADGSYTVNENKFNEIYKKLYSFTEIDLANKFKVKCRNTYFIKYGFLKVPNL LDDDIYTVSEGFNIGNLAVN NRGQNIKLNPKIIDSIPDKGLVEKIVKFCKSVIPRKGTKAPPRLCIRVNNRELFFVASES SYNENDINTPKEIDDTTNLN NNYRNNLDEVILDYNSETIPQISNQTLNTLVQDDSYVPRYDSNGTSEIEEHNVVDLNVFF YLHAQKVPEGETNISLTSSI   DTALSEESQVYTFFSSEFINTINKPVHAALFISWINQVIRDFTTEATQKSTFDKIADISL VVPYVGLALNIGNEVQKENF KEAFELLGAGILLEFVPELLIPTILVFTIKSFIGSSENKNKIIKAINNSLMERETKWKEI YSWIVSNWLTRINTQFNKRK EQMYQALQNQVDAIKTVIEYKYNNYTSDERNRLESEYNINNIREELNKKVSLAMENIERF ITESSIFYLMKLINEAKVSK LREYDEGVKEYLLDYISEHRSILGNSVQELNDLVTSTLNNSIPFELSSYTNDKILILYFN KLYKKIKDNSILDMRYENNK FIDISGYGSNISINGDVYIYSTNRNQFGIYSSKPSEVNIAQNNDIIYNGRYQNFSISFWV RIPKYFNKVNLNNEYTIIDC IRNNNSGWKISLNYNKIIWTLQDTAGNNQKLVFNYTQMISISDYINKWIFVTITNNRLGN SRIYINGNLIDEKSISNLGD IHVSDNILFKIVGCNDTRYVGIRYFKVFDTELGKTEIETLYSDEPDPSILKDFWGNYLLY NKRYYLLNLLRTDKSITQNS NFLNINQQRGVYQKPNIFSNTRLYTGVEVIIRKNGSTDISNTDNFVRKNDLAYINVVDRD VEYRLYADISIAKPEKIIKL IRTSNSNNSLGQIIVMDSIGNNCTMNFQNNNGGNIGLLGFHSNNLVASSWYYNNIRKNTS SNGCFWSFISKEHGWQEN   SEQ ID NO: 8 - BoNT/F7, amino acid sequence MPVNINNFNYNDPINNTTILYMKMPYYEDSNKYYKAFEIMDNVWIIPERNIIGKKPSDFY PPISLDSGSSAYYDPNYLTT DAEKDRFLKTVIKLFNRINSNPAGQVLLEEIKNGKPYLGNDHTAVNEFCANNRSTSVEIK ESKGTTDSMLLNLVILGPGP NILECSTFPVRIFPNNIAYDPSEKGFGSIQLMSFSTEYEYAFNDNTDLFIADPAISLAHE LIHVLHGLYGAKGVTNKKVI EVDQGALMAAEKDIKIEEFITFGGQDLNIITNSTNQKIYDNLLSNYTAIASRLSQVNINN SALNTTYYKNFFQWKYGLDQ DSNGNYTVNISKFNAIYKKLFSFTECDLAQKFQVKNRSNYLFHFKPFRLLDLLDDNIYSI SEGFNIGSLRVNNNGQNINL NSRIVGPIPDNGLVERFVGLCKSIVSKKGTKNSLCIKVNNRDLFFVASESSYNENGINSP KEIDDTTITNNNYKKNLDEV ILDYNSDAIPNLSSRLLNTTAQNDSYVPKYDSNGTSEIKEYTVDKLNVFFYLYAQKAPEG ESAISLTSSVNTALLDASKV YTFFSSDFINTVNKPVQAALFISWIQQVINDFTTEATQKSTIDKIADISLVVPYVGLALN IGNEVQKGNFKEAIELLGAG ILLEFVPELLIPTILVFTIKSFINSDDSKNKIIKAINNALRERELKWKEVYSWIVSNWLT RINTQFNKRKEQMYQALQNQ VDGIKKIIEYKYNNYTLDEKNRLKAEYNIYSIKEELNKKVSLAMQNIDRFLTESSISYLM KLINEAKINKLSEYDKRVNQ YLLNYILENSSTLGTSSVQELNNLVSNTLNNSIPFELSEYTNDKILISYFNRFYKRIIDS SILNMKYENNRFIDSSGYGS NISINGDIYIYSTNRNQFGIYSSRLSEVNITQNNTIIYNSRYQNFSVSFWVRIPKYNNLK NLNNEYTIINCMRNNNSGWK ISLNYNNIIWTLQDTTGNNQKLVFNYTQMIDISDYINKWTFVTITNNRLGHSKLYINGNL TDQKSILNLGNIHVDDNILF KIVGCNDTRYVGIRYFKIFNMELDKTEIETLYHSEPDSTILKDFWGNYLLYNKKYYLLNL LKPNMSVTKNSDILNINRQR GIYSKTNIFSNARLYTGVEVIIRKVGSTDTSNTDNFVRKNDTVYINVVDGNSEYQLYADV STSAVEKTIKLRRISNSNYN SNQMIIMDSIGDNCTMNFKTNNGNDIGLLGFHLNNLVASSWYYKNIRNNTRNNGCFWSFI SKEHGWQE   SEQ ID NO: 9 - BoNT/G, accession number WP_039635782, amino acid sequence MPVNIKNFNYNDPINNDDIIMMEPFNDPGPGTYYKAFRIIDRIWIVPERFTYGFQPDQFN ASTGVFSKDVYEYYDPTYLK TDAEKDKFLKTMIKLFNRINSKPSGQRLLDMIVDAIPYLGNASTPPDKFAANVANVSINK KIIQPGAEDQIKGLMTNLII FGPGPVLSDNFTDSMIMNGHSPISEGFGARMMIRFCPSCLNVFNNVQENKDTSIFSRRAY FADPALTLMHELIHVLHGLY GIKISNLPITPNTKEFFMQHSDPVQAEELYTFGGHDPSVISPSTDMNIYNKALQNFQDIA NRLNIVSSAQGSGIDISLYK QIYKNKYDFVEDPNGKYSVDKDKFDKLYKALMFGFTETNLAGEYGIKTRYSYFSEYLPPI KTEKLLDNTIYTQNEGFNIA SKNLKTEFNGQNKAVNKEAYEEISLEHLVIYRIAMCKPVMYKNTGKSEQCIIVNNEDLFF IANKDSFSKDLAKAETIAYN TQNNTIENNFSIDQLILDNDLSSGIDLPNENTEPFTNFDDIDIPVYIKQSALKKIFVDGD SLFEYLHAQTFPSNIENLQL TNSLNDALRNNNKVYTFFSTNLVEKANTVVGASLFVNWVKGVIDDFTSESTQKSTIDKVS DVSIIIPYIGPALNVGNETA KENFKNAFEIGGAAILMEFIPELIVPIVGFFTLESYVGNKGHIIMTISNALKKRDQKWTD MYGLIVSQWLSTVNTQFYTI KERMYNALNNQSQAIEKIIEDQYNRYSEEDKMNINIDFNDIDFKLNQSINLAINNIDDFI NQCSISYLMNRMIPLAVKKL KDFDDNLKRDLLEYIDTNELYLLDEVNILKSKVNRHLKDSIPFDLSLYTKDTILIQVFNN YISNISSNAILSLSYRGGRL IDSSGYGATMNVGSDVIFNDIGNGQFKLNNSENSNITAHQSKFVVYDSMFDNFSINFWVR TPKYNNNDIQTYLQNEYTII SCIKNDSGWKVSIKGNRIIWTLIDVNAKSKSIFFEYSIKDNISDYINKWFSITITNDRLG NANIYINGSLKKSEKILNLD RINSSNDIDFKLINCTDTTKFVWIKDFNIFGRELNATEVSSLYWIQSSTNTLKDFWGNPL RYDTQYYLFNQGMQNIYIKY FSKASMGETAPRTNFNNAAINYQNLYLGLRFIIKKASNSRNINNDNIVREGDYIYLNIDN ISDESYRVYVLVNSKEIQTQ LFLAPINDDPTFYDVLQIKKYYEKTTYNCQILCEKDTKTFGLFGIGKFVKDYGYVWDTYD NYFCISQWYLRRISENINKL RLGCNWQFIPVDEGWTE   SEQ ID NO: 10 - BoNT/DC, accession number BAM65681, amino acid sequence MTWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSK PPRPTSKYQSYYDPSYLSTD EQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEK FENGSWKVTNIITPSVLIFG PLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFC MDPVIALMHELTHSLHQLYG INIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGSDVEIIPQIERLQLREKALGHYKDI AKRLNNINKTIPSSWSSNID KYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSKHY LPVFANILDDNIYTIINGFN LTTKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCLRLTRNSRDDSTCIQVKNNTLPY VADKDSISQEIFESQIITDE TNVENYSDNFSLDESILDAKVPTNPEAVDPLLPNVNMEPLNVPGEEEVFYDDITKDVDYL NSYYYLEAQKLSNNVENITL TTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISD VSAIIPYIGPALNIGNSALR GNFKQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDS YQWMVSNWLSRITTQFNHIS YQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIR ECSVTYLFKNMLPKVIDELN KFDLKTKTELINLIDSHNIILVGEVDRLKAKVNESFENTIPFNIFSYTNNSLLKDMINEY FNSINDSKILSLQNKKNTLM DTSGYNAEVRVEGNVQLNPIFPFDFKLGSSGDDRGKVIVTQNENIVYNAMYESFSISFWI RINKWVSNLPGYTIIDSVKN NSGWSIGIISNFLVFTLKQNENSEQDINFSYDISKNAAGYNKWFFVTITTNMMGNMMIYI NGKLIDTIKVKELTGINFSK TITFQMNKIPNTGLITSDSDNINMWIRDFYIFAKELDDKDINILFNSLQYTNVVKDYWGN DLRYDKEYYMINVNYMNRYM SKKGNGIVFNTRKNNNDFNEGYKIIIKRIIGNTNDTRVRGENVLYFNTTIDNKQYSLGMY KPSRNLGTDLVPLGALDQPM   DEIRKYGSFIIQPCNTFDYYASQLFLSSNATTNRIGILSIGSYSFKLGDDYWFNHEYLIP VIKIEHYASLLESTSTHWVF VPASE   SEQ ID NO: 11 - BoNT/AB _MY , amino acid sequence MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERD 49 TFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIY 99 STDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEEL 149 NLVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEES 199 LEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFKVNTNA 249 YYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNK 299 AKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIY 349 TEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAA 399 NFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVRGIITSKTKSLDKGYNKA 449 LNDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLDLI 499 QQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNGKKYELDKYT 549 MFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATE 599 AAMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYK 649 DDFVGALIFSGAVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNAL 699 SKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAEATKAIINY 749 QYNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNS 799 MIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDI 849 PFQLSKYVDNQRLLSTFTEYIKNILNNIILNLRYKDNNLIDLSGYGAKVE 899 VYDGVELNDKNQFKLTSSANSKIRVTQNQNIIFNSVFLDFSVSFWIRIPK 949 YKNDGIQNYIHNEYTIINCMKNNSGWKISIRGNRIIWTLIDINGKTKSVF 999 FEYNIREDISEYINRWFFVTITNNLNNAKIYINGKLESNTDIKDIREVIA 1049 NGEIIFKLDGDIDRTQFIWMKYFSIFNTELSQSNIEERYKIQSYSEYLKD 1099 FWGNPLMYNKEYYMFNAGNKNSYIKLKKDSPVGEILTRSKYNQNSKYINY 1149 RDLYIGEKFIIRRKSNSQSINDDIVRKEDYIYLDFFNLNQEWRVYTYKYF 1199 KKEEMKLFLAPIYDSDEFYNTIQIKEYDEQPTYSCQLLFKKDEESTDEIG 1249 LIGIHRFYESGIVFEEYKDYFCISKWYLKEVKRKPYNLKLGCNWQFIPKD 1299 EGWTE 1304   SEQ ID NO: 12 – BoNT/X, amino acid sequence (GenBank: BAQ12790.1) MKLEINKFNYNDPIDGINVITMRPPRHSDKINKGKGPFKAFQVIKNIWIVPERYNFTNNT NDLNIPSEPIMEADAIYNPNYLN TPSEKDEFLQGVIKVLERIKSKPEGEKLLELISSSIPLPLVSNGALTLSDNETIAYQENN NIVSNLQANLVIYGPGPDIANNA TYGLYSTPISNGEGTLSEVSFSPFYLKPFDESYGNYRSLVNIVNKFVKREFAPDPASTLM HELVHVTHNLYGISNRNFYYNFD TGKIETSRQQNSLIFEELLTFGGIDSKAISSLIIKKIIETAKNNYTTLISERLNTVTVEN DLLKYIKNKIPVQGRLGNFKLDT AEFEKKLNTILFVLNESNLAQRFSILVRKHYLKERPIDPIYVNILDDNSYSTLEGFNISS QGSNDFQGQLLESSYFEKIESNA LRAFIKICPRNGLLYNAIYRNSKNYLNNIDLEDKKTTSKTNVSYPCSLLNGCIEVENKDL FLISNKDSLNDINLSEEKIKPET TVFFKDKLPPQDITLSNYDFTEANSIPSISQQNILERNEELYEPIRNSLFEIKTIYVDKL TTFHFLEAQNIDESIDSSKIRVE LTDSVDEALSNPNKVYSPFKNMSNTINSIETGITSTYIFYQWLRSIVKDFSDETGKIDVI DKSSDTLAIVPYIGPLLNIGNDI RHGDFVGAIELAGITALLEYVPEFTIPILVGLEVIGGELAREQVEAIVNNALDKRDQKWA EVYNITKAQWWGTIHLQINTRLA HTYKALSRQANAIKMNMEFQLANYKGNIDDKAKIKNAISETEILLNKSVEQAMKNTEKFM IKLSNSYLTKEMIPKVQDNLKNF DLETKKTLDKFIKEKEDILGTNLSSSLRRKVSIRLNKNIAFDINDIPFSEFDDLINQYKN EIEDYEVLNLGAEDGKIKDLSGT TSDINIGSDIELADGRENKAIKIKGSENSTIKIAMNKYLRFSATDNFSISFWIKHPKPTN LLNNGIEYTLVENFNQRGWKISI QDSKLIWYLRDHNNSIKIVTPDYIAFNGWNLITITNNRSKGSIVYVNGSKIEEKDISSIW NTEVDDPIIFRLKNNRDTQAFTL LDQFSIYRKELNQNEVVKLYNYYFNSNYIRDIWGNPLQYNKKYYLQTQDKPGKGLIREYW SSFGYDYVILSDSKTITFPNNIR YGALYNGSKVLIKNSKKLDGLVRNKDFIQLEIDGYNMGISADRFNEDTNYIGTTYGTTHD LTTDFEIIQRQEKYRNYCQLKTP YNIFHKSGLMSTETSKPTFHDYRDWVYSSAWYFQNYENLNLRKHTKTNWYFIPKDEGWDE D   SEQ ID NO: 13 (Nucleotide Sequence of Modified BoNT/A “Cat-A”) ATGCCATTCGTCAACAAGCAATTCAACTACAAAGACCCAGTCAACGGCGTCGACATCGCA TACATCAAGATTCCG AACGCCGGTCAAATGCAGCCGGTTAAGGCTTTTAAGATCCACAACAAGATTTGGGTTATC CCGGAGCGTGACACC TTCACGAACCCGGAAGAAGGCGATCTGAACCCGCCACCGGAAGCGAAGCAAGTCCCTGTC AGCTACTACGATTCG ACGTACCTGAGCACGGATAACGAAAAAGATAACTACCTGAAAGGTGTGACCAAGCTGTTC GAACGTATCTACAGC ACGGATCTGGGTCGCATGCTGCTGACTAGCATTGTTCGCGGTATCCCGTTCTGGGGTGGT AGCACGATTGACACC GAACTGAAGGTTATCGACACTAACTGCATTAACGTTATTCAACCGGATGGTAGCTATCGT AGCGAAGAGCTGAAT CTGGTCATCATTGGCCCGAGCGCAGACATTATCCAATTCGAGTGCAAGAGCTTTGGTCAC GAGGTTCTGAATCTG ACCCGCAATGGCTATGGTAGCACCCAGTACATTCGTTTTTCGCCGGATTTTACCTTCGGC TTTGAAGAGAGCCTG GAGGTTGATACCAATCCGTTGCTGGGTGCGGGCAAATTCGCTACCGATCCGGCTGTCACG CTGGCCCATGAACTG ATCCACGCAGGCCACCGCCTGTACGGCATTGCCATCAACCCAAACCGTGTGTTCAAGGTT AATACGAATGCATAC TACGAGATGAGCGGCCTGGAAGTCAGCTTCGAAGAACTGCGCACCTTCGGTGGCCATGAC GCTAAATTCATTGAC AGCTTGCAAGAGAATGAGTTCCGTCTGTACTACTATAACAAATTCAAAGACATTGCAAGC ACGTTGAACAAGGCC   AAAAGCATCGTTGGTACTACCGCGTCGTTGCAGTATATGAAGAATGTGTTTAAAGAGAAG TACCTGCTGTCCGAG GATACCTCCGGCAAGTTTAGCGTTGATAAGCTGAAGTTTGACAAACTGTACAAGATGCTG ACCGAGATTTACACC GAGGACAACTTTGTGAAATTCTTCAAAGTGTTGAATCGTAAAACCTATCTGAATTTTGAC AAAGCGGTTTTCAAG ATTAACATCGTGCCGAAGGTGAACTACACCATCTATGACGGTTTTAACCTGCGTAACACC AACCTGGCGGCGAAC TTTAACGGTCAGAATACGGAAATCAACAACATGAATTTCACGAAGTTGAAGAACTTCACG GGTCTGTTCGAGTTC TATAAGCTGCTGTGCGTGCGCGGTATCATCACCAGCAAAACCAAAAGCCTGGACAAAGGC TACAACAAGGCGCTG AATGACCTGTGCATTAAGGTAAACAATTGGGATCTGTTCTTTTCGCCATCCGAAGATAAT TTTACCAACGACCTG AACAAGGGTGAAGAAATCACCAGCGATACGAATATTGAAGCAGCGGAAGAGAATATCAGC CTGGATCTGATCCAG CAGTACTATCTGACCTTTAACTTCGACAATGAACCGGAGAACATTAGCATTGAGAATCTG AGCAGCGACATTATC GGTCAGCTGGAACTGATGCCGAATATCGAACGTTTCCCGAACGGCAAAAAGTACGAGCTG GACAAGTACACTATG TTCCATTACCTGCGTGCACAGGAGTTTGAACACGGTAAAAGCCGTATCGCGCTGACCAAC AGCGTTAACGAGGCC CTGCTGAACCCGAGCCGTGTCTATACCTTCTTCAGCAGCGACTATGTTAAGAAAGTGAAC AAAGCCACTGAGGCC GCGATGTTCCTGGGCTGGGTGGAACAGCTGGTATATGACTTCACGGACGAGACGAGCGAA GTGAGCACTACCGAC AAAATTGCTGATATTACCATCATTATCCCGTATATTGGTCCGGCACTGAACATTGGCAAC ATGCTGTACAAAGAC GATTTTGTGGGTGCCCTGATCTTCTCCGGTGCCGTGATTCTGCTGGAGTTCATTCCGGAG ATTGCGATCCCGGTG TTGGGTACCTTCGCGCTGGTGTCCTACATCGCGAATAAGGTTCTGACGGTTCAGACCATC GATAACGCGCTGTCG AAACGTAATGAAAAATGGGACGAGGTTTACAAATACATTGTTACGAATTGGCTGGCGAAA GTCAATACCCAGATC GACCTGATCCGTAAGAAAATGAAAGAGGCGCTGGAGAATCAGGCGGAGGCCACCAAAGCA ATTATCAACTACCAA TACAACCAGTACACGGAAGAAGAGAAGAATAACATTAACTTCAATATCGATGATTTGAGC AGCAAGCTGAATGAA TCTATCAACAAAGCGATGATCAATATCAACAAGTTTTTGAATCAGTGTAGCGTTTCGTAC CTGATGAATAGCATG ATTCCGTATGGCGTCAAACGTCTGGAGGACTTCGACGCCAGCCTGAAAGATGCGTTGCTG AAATACATTTACGAC AATCGTGGTACGCTGATTGGCCAAGTTGACCGCTTGAAAGACAAAGTTAACAATACCCTG AGCACCGACATCCCA TTTCAACTGAGCAAGTATGTTGATAATCAACGTCTGTTGAGCACTTTCACCGAGTATATC AAAAACATCATCAAT ACTAGCATTCTGAACCTGCGTTACGAGAGCAAGCATCTGATTGATCTGAGCCGTTATGCT AGCAAGATCAACATC GGTAGCAAGGTCAATTTTGACCCGATCGATAAGAACCAGATCCAGCTGTTTAATCTGGAA TCGAGCAAAATTGAG GTTATCCTGAAAAAGGCCATTGTCTACAACTCCATGTACGAGAATTTCTCCACCAGCTTC TGGATTCGCATCCCG AAATACTTCAACAAGATTAGCCTGAACAACGAGTATACTATCATCAACTGTATGGAGAAC AACAGCGGTTGGAAG GTGTCTCTGAACTATGGTGAGATCATTTGGACCTTGCAGGACACCAAAGAGATCAAGCAG CGCGTCGTGTTCAAG TACTCTCAAATGATCAACATTTCCGATTACATTAATCGTTGGATCTTCGTGACCATTACG AATAACCGTCTGAAT AAGAGCAAGATTTACATCAATGGTCGCTTGATCGATCAGAAACCGATTAGCAACCTGGGT AATATCCACGCAAGC AACAAGATTATGTTCAAATTGGACGGTTGCCGCGATACCCATCGTTATATCTGGATCAAG TATTTCAACCTGTTT GATAAAGAACTGAATGAGAAGGAGATCAAAGATTTGTATGACAACCAATCTAACAGCGGC ATTTTGAAGGACTTC TGGGGCGATTATCTGCAATACGATAAGCCGTACTATATGCTGAACCTGTATGATCCGAAC AAATATGTGGATGTC AATAATGTGGGTATTCGTGGTTACATGTATTTGAAGGGTCCGCGTGGCAGCGTTATGACG ACCAACATTTACCTG AACTCTAGCCTGTACCGTGGTACGAAATTCATCATTAAGAAATATGCCAGCGGCAACAAA GATAACATTGTGCGT AATAACGATCGTGTCTACATCAACGTGGTCGTGAAGAATAAAGAGTACCGTCTGGCGACC AACGCTTCGCAGGCG GGTGTTGAGAAAATTCTGAGCGCGTTGGAGATCCCTGATGTCGGTAATCTGAGCCAAGTC GTGGTTATGAAGAGC AAGAACGACAAGGGTATCACTAACAAGTGCAAGATGAACCTGCAAGACAACAATGGTAAC GACATCGGCTTTATT GGTTTCCACCAGTTCAACAATATTGCTAAACTGGTAGCGAGCAATTGGTACAATCGTCAG ATTGAGCGCAGCAGC cGTACTTTGGGCTGTAGCTGGGAGTTTATCCCGGTCGATGATGGTTGGGGCGAACGTCCG CTG SEQ ID NO: 14 (Polypeptide Sequence of Modified BoNT/A “Cat-A”) MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN PPPEAKQVPVSYYDS TYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCI NVIQPDGSYRSEELN LVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGA GKFATDPAVTLAHEL IHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLY YYNKFKDIASTLNKA KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV LNRKTYLNFDKAVFK INIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVRGII TSKTKSLDKGYNKAL NDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLDLIQQYYLTFNFDN EPENISIENLSSDII GQLELMPNIERFPNGKKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTF FSSDYVKKVNKATEA AMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSG AVILLEFIPEIAIPV LGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEA LENQAEATKAIINYQ YNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIPYGVKRLED FDASLKDALLKYIYD NRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKNIINTSILNLRYES KHLIDLSRYASKINI GSKVNFDPIDKNQIQLFNLESSKIEVILKKAIVYNSMYENFSTSFWIRIPKYFNKISLNN EYTIINCMENNSGWK VSLNYGEIIWTLQDTKEIKQRVVFKYSQMINISDYINRWIFVTITNNRLNKSKIYINGRL IDQKPISNLGNIHAS NKIMFKLDGCRDTHRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQYDKP YYMLNLYDPNKYVDV NNVGIRGYMYLKGPRGSVMTTNIYLNSSLYRGTKFIIKKYASGNKDNIVRNNDRVYINVV VKNKEYRLATNASQA GVEKILSALEIPDVGNLSQVVVMKSKNDKGITNKCKMNLQDNNGNDIGFIGFHQFNNIAK LVASNWYNRQIERSS RTLGCSWEFIPVDDGWGERPL   SEQ ID NO: 15 (Nucleotide Sequence of Modified BoNT/A “Cat-B”) ATGCCATTCGTCAACAAGCAATTCAACTACAAAGACCCAGTCAACGGCGTCGACATCGCA TACATCAAGATTCCG AACGCCGGTCAAATGCAGCCGGTTAAGGCTTTTAAGATCCACAACAAGATTTGGGTTATC CCGGAGCGTGACACC TTCACGAACCCGGAAGAAGGCGATCTGAACCCGCCACCGGAAGCGAAGCAAGTCCCTGTC AGCTACTACGATTCG ACGTACCTGAGCACGGATAACGAAAAAGATAACTACCTGAAAGGTGTGACCAAGCTGTTC GAACGTATCTACAGC ACGGATCTGGGTCGCATGCTGCTGACTAGCATTGTTCGCGGTATCCCGTTCTGGGGTGGT AGCACGATTGACACC GAACTGAAGGTTATCGACACTAACTGCATTAACGTTATTCAACCGGATGGTAGCTATCGT AGCGAAGAGCTGAAT CTGGTCATCATTGGCCCGAGCGCAGACATTATCCAATTCGAGTGCAAGAGCTTTGGTCAC GAGGTTCTGAATCTG ACCCGCAATGGCTATGGTAGCACCCAGTACATTCGTTTTTCGCCGGATTTTACCTTCGGC TTTGAAGAGAGCCTG GAGGTTGATACCAATCCGTTGCTGGGTGCGGGCAAATTCGCTACCGATCCGGCTGTCACG CTGGCCCATGAACTG ATCCACGCAGGCCACCGCCTGTACGGCATTGCCATCAACCCAAACCGTGTGTTCAAGGTT AATACGAATGCATAC TACGAGATGAGCGGCCTGGAAGTCAGCTTCGAAGAACTGCGCACCTTCGGTGGCCATGAC GCTAAATTCATTGAC AGCTTGCAAGAGAATGAGTTCCGTCTGTACTACTATAACAAATTCAAAGACATTGCAAGC ACGTTGAACAAGGCC AAAAGCATCGTTGGTACTACCGCGTCGTTGCAGTATATGAAGAATGTGTTTAAAGAGAAG TACCTGCTGTCCGAG GATACCTCCGGCAAGTTTAGCGTTGATAAGCTGAAGTTTGACAAACTGTACaAGATGCTG ACCGAGATTTACACC GAGGACAACTTTGTGAAATTCTTCAAAGTGTTGAATCGTAAAACCTATCTGAATTTTGAC AAAGCGGTTTTCAAG ATTAACATCGTGCCGAAGGTGAACTACACCATCTATGACGGTTTTAACCTGCGTAACACC AACCTGGCGGCGAAC TTTAACGGTCAGAATACGGAAATCAACAACATGAATTTCACGAAGTTGAAGAACTTCACG GGTCTGTTCGAGTTC TATAAGCTGCTGTGCGTGCGCGGTATCATCACCAGCAAAACCAAAAGCCTGGACAAAGGC TACAACAAGGCGCTG AATGACCTGTGCATTAAGGTAAACAATTGGGATCTGTTCTTTTCGCCATCCGAAGATAAT TTTACCAACGACCTG AACAAGGGTGAAGAAATCACCAGCGATACGAATATTGAAGCAGCGGAAGAGAATATCAGC CTGGATCTGATCCAG CAGTACTATCTGACCTTTAACTTCGACAATGAACCGGAGAACATTAGCATTGAGAATCTG AGCAGCGACATTATC GGTCAGCTGGAACTGATGCCGAATATCGAACGTTTCCCGAACGGCAAAAAGTACGAGCTG GACAAGTACACTATG TTCCATTACCTGCGTGCACAGGAGTTTGAACACGGTAAAAGCCGTATCGCGCTGACCAAC AGCGTTAACGAGGCC CTGCTGAACCCGAGCCGTGTCTATACCTTCTTCAGCAGCGACTATGTTAAGAAAGTGAAC AAAGCCACTGAGGCC GCGATGTTCCTGGGCTGGGTGGAACAGCTGGTATATGACTTCACGGACGAGACGAGCGAA GTGAGCACTACCGAC AAAATTGCTGATATTACCATCATTATCCCGTATATTGGTCCGGCACTGAACATTGGCAAC ATGCTGTACAAAGAC GATTTTGTGGGTGCCCTGATCTTCTCCGGTGCCGTGATTCTGCTGGAGTTCATTCCGGAG ATTGCGATCCCGGTG TTGGGTACCTTCGCGCTGGTGTCCTACATCGCGAATAAGGTTCTGACGGTTCAGACCATC GATAACGCGCTGTCG AAACGTAATGAAAAATGGGACGAGGTTTACAAATACATTGTTACGAATTGGCTGGCGAAA GTCAATACCCAGATC GACCTGATCCGTAAGAAAATGAAAGAGGCGCTGGAGAATCAGGCGGAGGCCACCAAAGCA ATTATCAACTACCAA TACAACCAGTACACGGAAGAAGAGAAGAATAACATTAACTTCAATATCGATGATTTGAGC AGCAAGCTGAATGAA TCTATCAACAAAGCGATGATCAATATCAACAAGTTTTTGAATCAGTGTAGCGTTTCGTAC CTGATGAATAGCATG ATTCCGTATGGCGTCAAACGTCTGGAGGACTTCGACGCCAGCCTGAAAGATGCGTTGCTG AAATACATTTACGAC AaTCGTGGTACGCTGATTGGCCAAGTTGACCGCTTGAAAGACAAAGTTAACAATACCCTG AGCACCGACATCCCA TTTCAACTGAGCAAGTATGTTGATAATCAACGTCTGTTGAGCACTTTCACCGAGTATATC AAAAACATCATCAAT ACTAGCATTCTGAACCTGCGTTACGAGAGCAATCATCTGATTGATCTGAGCCGTTATGCT AGCAAGATCAACATC GGTAGCAAGGTCAATTTTGACCCGATCGATAAGAACCAGATCCAGCTGTTTAATCTGGAA TCGAGCAAAATTGAG GTTATCCTGAAAAAGGCCATTGTCTACAACTCCATGTACGAGAATTTCTCCACCAGCTTC TGGATTCGCATCCCG AAATACTTCAAGAAGATTAGCCTGAACAACGAGTATACTATCATCAACTGTATGGAGAAC AACAGCGGTTGGAAG GTGTCTCTGAACTATGGTGAGATCATTTGGACCTTGCAGGACACCAAAGAGATCAAGCAG CGCGTCGTGTTCAAG TACTCTCAAATGATCAACATTTCCGATTACATTAATCGTTGGATCTTCGTGACCATTACG AATAACCGTCTGAAT AAGAGCAAGATTTACATCAATGGTCGCTTGATCGATCAGAAACCGATTAGCAACCTGGGT AATATCCACGCAAGC AACAAGATTATGTTCAAATTGGACGGTTGCCGCGATACCCATCGTTATATCTGGATCAAG TATTTCAACCTGTTT GATAAAGAACTGAATGAGAAGGAGATCAAAGATTTGTATGACAACCAATCTAACAGCGGC ATTTTGAAGGACTTC TGGGGCGATTATCTGCAATACGATAAGCCGTACTATATGCTGAACCTGTATGATCCGAAC AAATATGTGGATGTC AATAATGTGGGTATTCGTGGTTACATGTATTTGAAGGGTCCGCGTGGCAGCGTTATGACG ACCAACATTTACCTG AACTCTAGCCTGTACCGTGGTACGAAATTCATCATTAAGAAATATGCCAGCGGCAACAAA GATAACATTGTGCGT AATAACGATCGTGTCTACATCAACGTGGTCGTGAAGAATAAAGAGTACCGTCTGGCGACC AACGCTTCGCAGGCG GGTGTTGAGAAAATTCTGAGCGCGTTGGAGATCCCTGATGTCGGTAATCTGAGCCAAGTC GTGGTTATGAAGAGC AAGAACGACAAGGGTATCACTAACAAGTGCAAGATGAACCTGCAAGACAACAATGGTAAC GACATCGGCTTTATT GGTTTCCACCAGTTCAACAATATTGCTAAACTGGTAGCGAGCAATTGGTACAATCGTCAG ATTGAGCGCAGCAGC CGTACTTTGGGCTGTAGCTGGGAGTTTATCCCGGTCGATGATGGTTGGGGCGAACGTCCG CTG SEQ ID NO: 16 (Polypeptide Sequence of Modified BoNT/A “Cat-B”) MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN PPPEAKQVPVSYYDS TYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCI NVIQPDGSYRSEELN LVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGA GKFATDPAVTLAHEL IHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLY YYNKFKDIASTLNKA KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV LNRKTYLNFDKAVFK   INIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVRGII TSKTKSLDKGYNKAL NDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLDLIQQYYLTFNFDN EPENISIENLSSDII GQLELMPNIERFPNGKKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTF FSSDYVKKVNKATEA AMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSG AVILLEFIPEIAIPV LGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEA LENQAEATKAIINYQ YNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIPYGVKRLED FDASLKDALLKYIYD NRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKNIINTSILNLRYES NHLIDLSRYASKINI GSKVNFDPIDKNQIQLFNLESSKIEVILKKAIVYNSMYENFSTSFWIRIPKYFKKISLNN EYTIINCMENNSGWK VSLNYGEIIWTLQDTKEIKQRVVFKYSQMINISDYINRWIFVTITNNRLNKSKIYINGRL IDQKPISNLGNIHAS NKIMFKLDGCRDTHRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQYDKP YYMLNLYDPNKYVDV NNVGIRGYMYLKGPRGSVMTTNIYLNSSLYRGTKFIIKKYASGNKDNIVRNNDRVYINVV VKNKEYRLATNASQA GVEKILSALEIPDVGNLSQVVVMKSKNDKGITNKCKMNLQDNNGNDIGFIGFHQFNNIAK LVASNWYNRQIERSS RTLGCSWEFIPVDDGWGERPL SEQ ID NO: 17 (Nucleotide Sequence of Modified BoNT/A “Cat-C”) ATGCCATTCGTCAACAAGCAATTCAACTACAAAGACCCAGTCAACGGCGTCGACATCGCA TACATCAAGATTCCG AACGCCGGTCAAATGCAGCCGGTTAAGGCTTTTAAGATCCACAACAAGATTTGGGTTATC CCGGAGCGTGACACC TTCACGAACCCGGAAGAAGGCGATCTGAACCCGCCACCGGAAGCGAAGCAAGTCCCTGTC AGCTACTACGATTCG ACGTACCTGAGCACGGATAACGAAAAAGATAACTACCTGAAAGGTGTGACCAAGCTGTTC GAACGTATCTACAGC ACGGATCTGGGTCGCATGCTGCTGACTAGCATTGTTCGCGGTATCCCGTTCTGGGGTGGT AGCACGATTGACACC GAACTGAAGGTTATCGACACTAACTGCATTAACGTTATTCAACCGGATGGTAGCTATCGT AGCGAAGAGCTGAAT CTGGTCATCATTGGCCCGAGCGCAGACATTATCCAATTCGAGTGCAAGAGCTTTGGTCAC GAGGTTCTGAATCTG ACCCGCAATGGCTATGGTAGCACCCAGTACATTCGTTTTTCGCCGGATTTTACCTTCGGC TTTGAAGAGAGCCTG GAGGTTGATACCAATCCGTTGCTGGGTGCGGGCAAATTCGCTACCGATCCGGCTGTCACG CTGGCCCATGAACTG ATCCACGCAGGCCACCGCCTGTACGGCATTGCCATCAACCCAAACCGTGTGTTCAAGGTT AATACGAATGCATAC TACGAGATGAGCGGCCTGGAAGTCAGCTTCGAAGAACTGCGCACCTTCGGTGGCCATGAC GCTAAATTCATTGAC AGCTTGCAAGAGAATGAGTTCCGTCTGTACTACTATAACAAATTCAAAGACATTGCAAGC ACGTTGAACAAGGCC AAAAGCATCGTTGGTACTACCGCGTCGTTGCAGTATATGAAGAATGTGTTTAAAGAGAAG TACCTGCTGTCCGAG GATACCTCCGGCAAGTTTAGCGTTGATAAGCTGAAGTTTGACAAACTGTACAAGATGCTG ACCGAGATTTACACC GAGGACAACTTTGTGAAATTCTTCAAAGTGTTGAATCGTAAAACCTATCTGAATTTTGAC AAAGCGGTTTTCAAG ATTAACATCGTGCCGAAGGTGAACTACACCATCTATGACGGTTTTAACCTGCGTAACACC AACCTGGCGGCGAAC TTTAACGGTCAGAATACGGAAATCAACAACATGAATTTCACGAAGTTGAAGAACTTCACG GGTCTGTTCGAGTTC TATAAGCTGCTGTGCGTGCGCGGTATCATCACCAGCAAAACCAAAAGCCTGGACAAAGGC TACAACAAGGCGCTG AATGACCTGTGCATTAAGGTAAACAATTGGGATCTGTTCTTTTCGCCATCCGAAGATAAT TTTACCAACGACCTG AACAAGGGTGAAGAAATCACCAGCGATACGAATATTGAAGCAGCGGAAGAGAATATCAGC CTGGATCTGATCCAG CAGTACTATCTGACCTTTAACTTCGACAATGAACCGGAGAACATTAGCATTGAGAATCTG AGCAGCGACATTATC GGTCAGCTGGAACTGATGCCGAATATCGAACGTTTCCCGAACGGCAAAAAGTACGAGCTG GACAAGTACACTATG TTCCATTACCTGCGTGCACAGGAGTTTGAACACGGTAAAAGCCGTATCGCGCTGACCAAC AGCGTTAACGAGGCC CTGCTGAACCCGAGCCGTGTCTATACCTTCTTCAGCAGCGACTATGTTAAGAAAGTGAAC AAAGCCACTGAGGCC GCGATGTTCCTGGGCTGGGTGGAACAGCTGGTATATGACTTCACGGACGAGACGAGCGAA GTGAGCACTACCGAC AAAATTGCTGATATTACCATCATTATCCCGTATATTGGTCCGGCACTGAACATTGGCAAC ATGCTGTACAAAGAC GATTTTGTGGGTGCCCTGATCTTCTCCGGTGCCGTGATTCTGCTGGAGTTCATTCCGGAG ATTGCGATCCCGGTG TTGGGTACCTTCGCGCTGGTGTCCTACATCGCGAATAAGGTTCTGACGGTTCAGACCATC GATAACGCGCTGTCG AAACGTAATGAAAAATGGGACGAGGTTTACAAATACATTGTTACGAATTGGCTGGCGAAA GTCAATACCCAGATC GACCTGATCCGTAAGAAAATGAAAGAGGCGCTGGAGAATCAGGCGGAGGCCACCAAAGCA ATTATCAACTACCAA TACAACCAGTACACGGAAGAAGAGAAGAATAACATTAACTTCAATATCGATGATTTGAGC AGCAAGCTGAATGAA TCTATCAACAAAGCGATGATCAATATCAACAAGTTTTTGAATCAGTGTAGCGTTTCGTAC CTGATGAATAGCATG ATTCCGTATGGCGTCAAACGTCTGGAGGACTTCGACGCCAGCCTGAAAGATGCGTTGCTG AAATACATTTACGAC AATCGTGGTACGCTGATTGGCCAAGTTGACCGCTTGAAAGACAAAGTTAACAATACCCTG AGCACCGACATCCCA TTTCAACTGAGCAAGTATGTTGATAATCAACGTCTGTTGAGCACTTTCACCGAGTATATC AAAAACATCATCAAT ACTAGCATTCTGAACCTGCGTTACGAGAGCAATCATCTGATTGATCTGAGCCGTTATGCT AGCAAGATCAACATC GGTAGCAAGGTCAATTTTGACCCGATCGATAAGAACCAGATCCAGCTGTTTAATCTGGAA TCGAGCAAAATTGAG GTTATCCTGAAAAAGGCCATTGTCTACAACTCCATGTACGAGAATTTCTCCACCAGCTTC TGGATTCGCATCCCG AAATACTTCAACAAGATTAGCCTGAACAACGAGTATACTATCATCAACTGTATGGAGAAC AACAGCGGTTGGAAG GTGTCTCTGAACTATGGTGAGATCATTTGGACCTTGCAGGACACCAAAGAGATCAAGCAG CGCGTCGTGTTCAAG TACTCTCAAATGATCAACATTTCCGATTACATTAATCGTTGGATCTTCGTGACCATTACG AATAACCGTCTGAAG AAGAGCAAGATTTACATCAATGGTCGCTTGATCGATCAGAAACCGATTAGCAACCTGGGT AATATCCACGCAAGC AACAAGATTATGTTCAAATTGGACGGTTGCCGCGATACCCATCGTTATATCTGGATCAAG TATTTCAACCTGTTT GATAAAGAACTGAATGAGAAGGAGATCAAAGATTTGTATGACAACCAATCTAACAGCGGC ATTTTGAAGGACTTC TGGGGCGATTATCTGCAATACGATAAGCCGTACTATATGCTGAACCTGTATGATCCGAAC AAATATGTGGATGTC   AATAATGTGGGTATTCGTGGTTACATGTATTTGAAGGGTCCGCGTGGCAGCGTTATGACG ACCAACATTTACCTG AACTCTAGCCTGTACCGTGGTACGAAATTCATCATTAAGAAATATGCCAGCGGCAACAAA GATAACATTGTGCGT AATAACGATCGTGTCTACATCAACGTGGTCGTGAAGAATAAAGAGTACCGTCTGGCGACC AACGCTTCGCAGGCG GGTGTTGAGAAAATTCTGAGCGCGTTGGAGATCCCTGATGTCGGTAATCTGAGCCAAGTC GTGGTTATGAAGAGC AAGAACGACAAGGGTATCACTAACAAGTGCAAGATGAACCTGCAAGACAACAATGGTAAC GACATCGGCTTTATT GGTTTCCACCAGTTCAACAATATTGCTAAACTGGTAGCGAGCAATTGGTACAATCGTCAG ATTGAGCGCAGCAGC CGTACTTTGGGCTGTAGCTGGGAGTTTATCCCGGTCGATGATGGTTGGGGCGAACGTCCG CTG SEQ ID NO: 18 (Polypeptide Sequence of Modified BoNT/A “Cat-C”) MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN PPPEAKQVPVSYYDS TYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCI NVIQPDGSYRSEELN LVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGA GKFATDPAVTLAHEL IHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLY YYNKFKDIASTLNKA KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV LNRKTYLNFDKAVFK INIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVRGII TSKTKSLDKGYNKAL NDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLDLIQQYYLTFNFDN EPENISIENLSSDII GQLELMPNIERFPNGKKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTF FSSDYVKKVNKATEA AMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSG AVILLEFIPEIAIPV LGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEA LENQAEATKAIINYQ YNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIPYGVKRLED FDASLKDALLKYIYD NRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKNIINTSILNLRYES NHLIDLSRYASKINI GSKVNFDPIDKNQIQLFNLESSKIEVILKKAIVYNSMYENFSTSFWIRIPKYFNKISLNN EYTIINCMENNSGWK VSLNYGEIIWTLQDTKEIKQRVVFKYSQMINISDYINRWIFVTITNNRLKKSKIYINGRL IDQKPISNLGNIHAS NKIMFKLDGCRDTHRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQYDKP YYMLNLYDPNKYVDV NNVGIRGYMYLKGPRGSVMTTNIYLNSSLYRGTKFIIKKYASGNKDNIVRNNDRVYINVV VKNKEYRLATNASQA GVEKILSALEIPDVGNLSQVVVMKSKNDKGITNKCKMNLQDNNGNDIGFIGFHQFNNIAK LVASNWYNRQIERSS RTLGCSWEFIPVDDGWGERPL SEQ ID NO: 19 (Nucleotide Sequence of Modified BoNT/A “Cat-D”) ATGCCATTCGTCAACAAGCAATTCAACTACAAAGACCCAGTCAACGGCGTCGACATCGCA TACATCAAGATTCCG AACGCCGGTCAAATGCAGCCGGTTAAGGCTTTTAAGATCCACAACAAGATTTGGGTTATC CCGGAGCGTGACACC TTCACGAACCCGGAAGAAGGCGATCTGAACCCGCCACCGGAAGCGAAGCAAGTCCCTGTC AGCTACTACGATTCG ACGTACCTGAGCACGGATAACGAAAAAGATAACTACCTGAAAGGTGTGACCAAGCTGTTC GAACGTATCTACAGC ACGGATCTGGGTCGCATGCTGCTGACTAGCATTGTTCGCGGTATCCCGTTCTGGGGTGGT AGCACGATTGACACC GAACTGAAGGTTATCGACACTAACTGCATTAACGTTATTCAACCGGATGGTAGCTATCGT AGCGAAGAGCTGAAT CTGGTCATCATTGGCCCGAGCGCAGACATTATCCAATTCGAGTGCAAGAGCTTTGGTCAC GAGGTTCTGAATCTG ACCCGCAATGGCTATGGTAGCACCCAGTACATTCGTTTTTCGCCGGATTTTACCTTCGGC TTTGAAGAGAGCCTG GAGGTTGATACCAATCCGTTGCTGGGTGCGGGCAAATTCGCTACCGATCCGGCTGTCACG CTGGCCCATGAACTG ATCCACGCAGGCCACCGCCTGTACGGCATTGCCATCAACCCAAACCGTGTGTTCAAGGTT AATACGAATGCATAC TACGAGATGAGCGGCCTgGAAGTCAGCTTCGAAGAACTGCGCACCTTCGGTGGCCATGAC GCTAAATTCATTGAC AGCTTGCAAGAGAATGAGTTCCGTCTGTACTACTATAACAAATTCAAAGACATTGCAAGC ACGTTGAACAAGGCC AAAAGCATCGTTGGTACTACCGCGTCGTTGCAGTATATGAAGAATGTGTTTAAAGAGAAG TACCTGCTGTCCGAG GATACCTCCGGCAAGTTTAGCGTTGATAAGCTGAAGTTTGACAAACTGTACAAGATGCTG ACCGAGATTTACACC GAGGACAACTTTGTGAAATTCTTCAAaGTGTTGAATCGTAAAACCTATCTGAATTTTGAC AAAGCGGTTTTCaAG ATTAACATCGTGCCGAAGGTGAACTACACCATCTATGACGGTTTTAACCTGCGTAACACC AACCTGGCGGCGAAC TTTAACGGTCAGAATACGGAAATCAACAACATGAATTTCACGAAGTTGAAGAACTTCACG GGTCTGTTCGAGTTC TATAAGCTGCTGTGCGTGCGCGGTATCATCACCAGCAAAACCAAAAGCCTGGACAAAGGC TACAACAAGGCGCTG AATGACCTGTGCATTAAGGTAAACAATTGGGATCTGTTCTTTTCGCCATCCGAAGATAAT TTTACCAACGACCTG AACAAGGGTGAAGAAATCACCAGCGATACGAATATTGAAGCAGCGGAAGAGAATATCAGC CTGGATCTGATCCAG CAGTACTATCTGACCTTTAACTTCGACAATGAACCGGAGAACATTAGCATTGAGAATCTG AGCAGCGACATTATC GGTCAGCTGGAACTGATGCCGAATATCGAACGTTTCCCGAACGGCAAAAAGTACGAGCTG GACAAGTACACTATG TTCCATTACCTGCGTGCACAGGAGTTTGAACACGGTAAAAGCCGTATCGCGCTGACCAAC AGCGTTAACGAGGCC CTGCTGAACCCGAGCCGTGTCTATACCTTCTTCAGCAGCGACTATGTTAAGAAAGTGAAC AAAGCCACTGAGGCC GCGATGTTCCTGGGCTGGGTGGAACAGCTGGTATATGACTTCACGGACGAGACGAGCGAA GTGAGCACTACCGAC AAAaTTGCTGATaTTACCATCATTATCCCGTATATTGGTCCGGCACTGAACATTGGCAAC ATGCTGTACAAAGAC GATTTTGTGGGTGCCCTGATCTTCTCCGGTGCCGTGATTCTGCTGGAGTTCATTCCGGAG ATTGCGATCCCGGTG TTGGGTACCTTCGCGCTGGTGTCCTACATCGCGAATAAGGTTCTGACGGTTCAGACCATC GATAACGCGCTGTCG AAACGTAATGAAAAATGGGACGAGGTTTACAAATACATTGTTACGAATTGGCTGGCGAAA GTCaATACCCAGATC GACCTGATCCGTAAGAAAATGAAAGAGGCGCTGGAGAATCAGGCGGAGGCCACCAAAGCA ATTATCAACTACCAA TACAACCAGTACACGGAAGAAGAGAAGAATAACATTAACTTCAATATCGATGATTTGAGC AGCAAGCTGAATGAA   TCTATCAACAAAGCGATGATCAATATCAACAAGTTTTTGAATCAGTGTAGCGTTTCGTAC CTGATGAATAGCATG ATTCCGTATGGCGTCAAACGTCTGGAGGACTTCGACGCCAGCCTGAAAGATGCGTTGCTG AAATACATTTACGAC AATCGTGGTACGCTGATTGGCCAAGTTGACCGCTTGAAAGACAAAGTTAACAATACCCTG AGCACCGACATCCCA TTTCAACTGAGCAAGTATGTTGATAATCAACGTCTGTTGAGCACTTTCACCGAGTATATC AAAAACATCATCAAT ACTAGCATTCTGAACCTGCGTTACGAGAGCAATCATCTGATtGATCTGAGCCGTTATGCA AGCAAGATCAACATC GGTAGCAAGGTCAATTTTGACCCGATCGATAAGAACCAGATCCAGCTGTTTAATCTGGAA TCGAGCAAAATTGAG GTTATCCTGAAAAACGCCATTGTCTACAACTCCATGTACGAGAATTTCTCCACCAGCTTC TGGATTCGCATCCCG AAATACTTCAACAGCATTAGCCTGAACAACGAGTATACTATCATCAACTGTATGGAGAAC AACAGCGGTTGGAAG GTGTCTCTGAACTATGGTGAGATCATTTGGACCTTGCAGGACACCCAAGAGATCAAGCAG CGCGTCGTGTTCAAG TACTCTCAAATGATCAACATTTCCGATTACATTAATCGTTGGATCTTCGTGACCATTACG AATAACCGTCTGAAT AACAGCAAGATTTACATCAATGGTCGCTTGATCGATCAGAAACCGATTAGCAACCTGGGT AATATCCACGCAAGC AACAACATTATGTTCAAATTGGACGGTTGCCGCGATACCCATCGTTATATCTGGATCAAG TATTTCAACCTGTTT GATAAAGAACTGAATGAGAAGGAGATCAAAGATTTGTATGACAACCAATCTAACAGCGGC ATTTTGAAGGACTTC TGGGGCGATTATCTGCAATACGATAAGCCGTACTATATGCTGAACCTGTATGATCCGAAC AAATATGTGGATGTC AATAATGTGGGTATTCGTGGTTACATGTATTTGAAGGGTCCGCGTGGCAGCGTTATGACG ACCAACATTTACCTG AACTCTAGCCTGTACCGTGGTACGAAATTCATCATTAAGAAATATGCCAGCGGCAACAAA GATAACATTGTGCGT AATAACGATCGTGTCTACATCAACGTGGTCGTGAAGCGTAAAGAGTACCGTCTGGCGACC AACGCTTCGCAGGCG GGTGTTGAGAAAATTCTGAGCGCGTTGGAGATCCCTCGTGTCCGTCGTCTGAGCCAAGTC GTGGTTATGAAGAGC AAGAACGACCAGGGTATCACTAACAAGTGCAAGATGAACCTGCAAGACCGTCGTGGTAAC GACATCGGCTTTATT GGTTTCCACCAGTTCAACAATATTGCTAAACTGGTAGCGAGCAATTGGTACAATCGTCAG ATTGAGCGCCGTAGC CGTCGTTTGGGCTGTAGCTGGGAGTTTATCCCGGTCGATGATGGTTGGGGCGAACGTCCG CTG SEQ ID NO: 20 (Polypeptide Sequence of Modified BoNT/A “Cat-D”) MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN PPPEAKQVPVSYYDS TYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCI NVIQPDGSYRSEELN LVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGA GKFATDPAVTLAHEL IHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLY YYNKFKDIASTLNKA KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV LNRKTYLNFDKAVFK INIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVRGII TSKTKSLDKGYNKAL NDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLDLIQQYYLTFNFDN EPENISIENLSSDII GQLELMPNIERFPNGKKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTF FSSDYVKKVNKATEA AMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSG AVILLEFIPEIAIPV LGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEA LENQAEATKAIINYQ YNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIPYGVKRLED FDASLKDALLKYIYD NRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKNIINTSILNLRYES NHLIDLSRYASKINI GSKVNFDPIDKNQIQLFNLESSKIEVILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNN EYTIINCMENNSGWK VSLNYGEIIWTLQDTQEIKQRVVFKYSQMINISDYINRWIFVTITNNRLNNSKIYINGRL IDQKPISNLGNIHAS NNIMFKLDGCRDTHRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQYDKP YYMLNLYDPNKYVDV NNVGIRGYMYLKGPRGSVMTTNIYLNSSLYRGTKFIIKKYASGNKDNIVRNNDRVYINVV VKRKEYRLATNASQA GVEKILSALEIPRVRRLSQVVVMKSKNDQGITNKCKMNLQDRRGNDIGFIGFHQFNNIAK LVASNWYNRQIERRS RRLGCSWEFIPVDDGWGERPL SEQ ID NO: 21 (Polypeptide Sequence of Modified BoNT/A “Chimera 1”) MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN PPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGG STIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGY GSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPN RVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKA KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV LNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFT GLFEFYKLLCVRGIITSKTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEE ITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNG KKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEA AMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSG AVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAK VNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKA MININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDK VNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKSEILNNIILNLRYKDNNLIDLSGYGAKVE   VYDGVELNDKNQFKLTSSANSKIRVTQNQNIIFNSVFLDFSVSFWIRIPKYKNDGIQNYI HNEYTIINCMKNNSGWKISIRGNRIIWTLIDINGKTKSVFFEYNIREDISEYINRWFFVT ITNNLNNAKIYINGKLESNTDIKDIREVIANGEIIFKLDGDIDRTQFIWMKYFSIFNTEL SQSNIEERYKIQSYSEYLKDFWGNPLMYNKEYYMFNAGNKNSYIKLKKDSPVGEILTRSK YNQNSKYINYRDLYIGEKFIIRRKSNSQSINDDIVRKEDYIYLDFFNLNQEWRVYTYKYF KKEEMKLFLAPIYDSDEFYNTIQIKEYDEQPTYSCQLLFKKDEESTDEIGLIGIHRFYES GIVFEEYKDYFCISKWYLKEVKRKPYNLKLGCNWQFIPKDEGWTEHHHHHHHHHH SEQ ID NO: 22 (Polypeptide Sequence of Modified BoNT/A “Chimera 2”) MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN PPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGG STIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGY GSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPN RVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKA KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV LNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFT GLFEFYKLLCVRGIITSKTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEE ITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNG KKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEA AMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSG AVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAK VNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKA MININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDK VNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKNIIELGGGGSELSEILNNIILNLRYKDNN LIDLSGYGAKVEVYDGVELNDKNQFKLTSSANSKIRVTQNQNIIFNSVFLDFSVSFWIRI PKYKNDGIQNYIHNEYTIINCMKNNSGWKISIRGNRIIWTLIDINGKTKSVFFEYNIRED ISEYINRWFFVTITNNLNNAKIYINGKLESNTDIKDIREVIANGEIIFKLDGDIDRTQFI WMKYFSIFNTELSQSNIEERYKIQSYSEYLKDFWGNPLMYNKEYYMFNAGNKNSYIKLKK DSPVGEILTRSKYNQNSKYINYRDLYIGEKFIIRRKSNSQSINDDIVRKEDYIYLDFFNL NQEWRVYTYKYFKKEEMKLFLAPIYDSDEFYNTIQIKEYDEQPTYSCQLLFKKDEESTDE IGLIGIHRFYESGIVFEEYKDYFCISKWYLKEVKRKPYNLKLGCNWQFIPKDEGWTEHHH HHHHHHH SEQ ID NO: 23 (Polypeptide Sequence of Modified BoNT/A “Chimera 3A”) MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN PPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGG STIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGY GSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPN RVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKA KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV LNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFT GLFEFYKLLCVRGIITSKTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEE ITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNG KKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEA AMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSG AVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAK VNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKA MININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDK VNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKNILNNIILNLRYKDNNLIDLSGYGAKVEV YDGVELNDKNQFKLTSSANSKIRVTQNQNIIFNSVFLDFSVSFWIRIPKYKNDGIQNYIH NEYTIINCMKNNSGWKISIRGNRIIWTLIDINGKTKSVFFEYNIREDISEYINRWFFVTI TNNLNNAKIYINGKLESNTDIKDIREVIANGEIIFKLDGDIDRTQFIWMKYFSIFNTELS QSNIEERYKIQSYSEYLKDFWGNPLMYNKEYYMFNAGNKNSYIKLKKDSPVGEILTRSKY NQNSKYINYRDLYIGEKFIIRRKSNSQSINDDIVRKEDYIYLDFFNLNQEWRVYTYKYFK   KEEMKLFLAPIYDSDEFYNTIQIKEYDEQPTYSCQLLFKKDEESTDEIGLIGIHRFYESG IVFEEYKDYFCISKWYLKEVKRKPYNLKLGCNWQFIPKDEGWTEHHHHHHHHHH SEQ ID NO: 24 (Polypeptide Sequence of Modified BoNT/A “Chimera 3B”) MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN PPPEAKQVPVSYYDS TYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCI NVIQPDGSYRSEELN LVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGA GKFATDPAVTLAHEL IHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLY YYNKFKDIASTLNKA KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV LNRKTYLNFDKAVFK INIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVRGII TSKTKSLDKGYNKAL NDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLDLIQQYYLTFNFDN EPENISIENLSSDII GQLELMPNIERFPNGKKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTF FSSDYVKKVNKATEA AMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSG AVILLEFIPEIAIPV LGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEA LENQAEATKAIINYQ YNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIPYGVKRLED FDASLKDALLKYIYD NRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKNILNNIILNLRYKD NNLIDLSGYGAKVEV YDGVELNDKNQFKLTSSANSKIRVTQNQNIIFNSVFLDFSVSFWIRIPKYKNDGIQNYIH NEYTIINCMKNNSGW KISIRGNRIIWTLIDINGKTKSVFFEYNIREDISEYINRWFFVTITNNLNNAKIYINGKL ESNTDIKDIREVIAN GEIIFKLDGDIDRTQFIWMKYFSIFNTELSQSNIEERYKIQSYSEYLKDFWGNPLMYNKE YYMFNAGNKNSYIKL KKDSPVGEILTRSKYNQNSKYINYRDLYIGEKFIIRRKSNSQSINDDIVRKEDYIYLDFF NLNQEWRVYTYKYFK KEEMKLFLAPIYDSDEFYNTIQIKEYDEQPTYSCQLLFKKDEESTDEIGLIGIHRFYESG IVFEEYKDYFCISKW YLKEVKRKPYNLKLGCNWQFIPKDEGWTE SEQ ID NO: 25 (Polypeptide Sequence of Modified BoNT/A “Chimera 3C”) MPFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN PPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGG STIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGY GSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPN RVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKA KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV LNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFT GLFEFYKLLCVRGIITSKTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEE ITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNG KKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEA AMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSG AVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAK VNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKA MININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDK VNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKNILNNIILNLRYKDNNLIDLSGYGAKVEV YDGVELNDKNQFKLTSSANSKIRVTQNQNIIFNSVFLDFSVSFWIRIPKYKNDGIQNYIH NEYTIINCMKNNSGWKISIRGNRIIWTLIDINGKTKSVFFEYNIREDISEYINRWFFVTI TNNLNNAKIYINGKLESNTDIKDIREVIANGEIIFKLDGDIDRTQFIWMKYFSIFNTELS QSNIEERYKIQSYSEYLKDFWGNPLMYNKEYYMFNAGNKNSYIKLKKDSPVGEILTRSKY NQNSKYINYRDLYIGEKFIIRRKSNSQSINDDIVRKEDYIYLDFFNLNQEWRVYTYKYFK KEEEKLFLAPISDSDEFYNTIQIKEYDEQPTYSCQLLFKKDEESTDEIGLIGIHRFYESG IVFEEYKDYFCISKWYLKEVKRKPYNLKLGCNWQFIPKDEGWTE SEQ ID NO: 26 (TEV Cleavage Site) ENLYFQG SEQ ID NO: 27 (Thrombin Cleavage Site) LVPRGS SEQ ID NO: 28 (PreScission Cleavage Site) LEVLFQGP   SEQ ID NO: 29 (Enterokinase Cleavage Site) DDDDK SEQ ID NO: 30 (Factor Xa Cleavage Site 1) IEGR SEQ ID NO: 31 (Factor Xa Cleavage Site 2) IDGR SEQ ID NO: 32 (Influenza Virus Haemagglutinin) GLFGAIAGFIENGWEGMIDGWYG EXAMPLES MATERIALS AND METHODS Animal model Rats treated with cyclophosphamide (CYP) were used in the following study. A chronic rat model of CYP-induced BPS/IC was developed consisting of 3 injections (40 mg/kg, i.p.) every 3 days. For example, Augé C, et al. Characterization and Validation of a Chronic Model of Cyclophosphamide-Induced Interstitial Cystitis/Bladder Pain Syndrome in Rats. Front Pharmacol.2020 Aug 28;11:1305. doi: 10.3389/fphar.2020.01305. PMID: 32982733; PMCID: PMC7485435 and Zhang HP, et al. The function of P2X3 receptor and NK1 receptor antagonists on cyclophosphamide-induced cystitis in rats. World J Urol.2014 Feb;32(1):91-7. doi: 10.1007/s00345-013-1098-z. Epub 2013 May 12. PMID: 23666265 describe a CYP- induced BPS/IC model. No severe weight loss occurred. This model shows long-lasting visceral pain which is characterized by both allodynia (painful response to a normally innocuous stimulus) and hyperalgesia (increased response to a noxious stimulus). Induction of chronic cystitis To induce chronic cystitis, at Day 0 (D0), D3 and D6, rats were weighted and an intraperitoneal (i.p.) injection of CYP at a dose of 40 mg/kg in a final volume of 5 mL/kg was performed. CYP was prepared fresh in saline at a final concentration of 8 mg/mL. Control rats received physiological saline under the same experimental conditions as CYP. Von Frey assay Visceral pain was assessed using the Von Frey assay. For example, Garrido-Suarez, B et al., (2015). Ovariectomy-induced chronic abdominal hypernociception in rats: Relation with brain oxidative stress. Journal of Pharmacy & Pharmacognosy Research.3.148-161 and Deuis JR, et al., Methods Used to Evaluate Pain Behaviors in Rodents. Front Mol Neurosci.2017 Sep   6;10:284. doi: 10.3389/fnmol.2017.00284. PMID: 28932184; PMCID: PMC5592204 describe the Von Frey assay methodology. Standardized conditions including single-experimenter testing of all animals were applied to minimize variability behaviour-based pain testing. Visceral pain was evaluated in a blinded manner by applying to the lower abdomen, close to the urinary bladder, a set of 8 calibrated Von Frey filaments of increasing forces (1, 2, 4, 6, 8, 10, 15 and 26 g) with an interstimulus interval of 5 seconds. Prior to testing, the abdominal area designed for mechanical stimulation of each animal was shaved. Animals were placed on a raised wire mesh floor under individual transparent Plexiglas box and acclimatized for at least 30 minutes before starting the Von Frey test. Filaments were then applied for 1-2 seconds through the mesh floor with enough strength to cause the filament to slightly bend. Each filament was tested 3 times. Care was taken to stimulate different areas within the lower abdominal region in the vicinity of the urinary bladder to avoid desensitization. Nociceptive behaviours were scored for each animal and each filament as shown in table 1. Table 1 – scoring of nociceptive behaviours Expression and analysis of results Visceral pain Definitions of the nociceptive parameters are provided in table 2. Table 2 – definitions of nociceptive parameters   1 at the second and 2 at the third, the summation of its scores is 4. The maximal pooled score being 9 (3 + 3 + 3), a pooled score of 4 equals 44% of the maximal response (100 x 4/9). EXAMPLE 1 Protocol design The following protocol was carried out (and as shown in Figure 5) to assess the effects of Dysport on a chronic rat model of CYP-induced BPS/IC. • At D-1, rats were acclimatized to the individual Plexiglas box (Von Frey set up) for a minimum of 30 min and to the application of the Von Frey filaments, in order to decrease the level of stress due to the new environment. • At D0, before CYP or saline first injection Von Frey testing was performed in order to obtain basal values for nociceptive behaviour. • At D0, D3 and D6, chronic cystitis was induced to mimic BPS/IC. • At D7 (before treatments start), von Frey testing was performed to assess chronic cystitis induction. • At D8, pharmacological i.ves. treatment was performed. • At D10 and D12, von Frey testing was performed to analyze the effects of test (Dysport) and reference substances (DMSO and laluril) on CYP-induced chronic visceral pain. Substances Reconstitution of Dysport On each day of experimentation, a vial containing 500 U of Dysport was solubilized in 1 mL of sterile phosphate buffered saline (PBS) to obtain a final concentration of 500 U/mL. The master solution was diluted 8.33-, 12.5-, or 25-fold in vehicle to obtain the 30, 20 or 10 U/500 μL, respectively. Dilutions were performed in silicon glass tubes (batch n° 8072554, Becton- Dickinson, Plymouth, UK).   Vehicle Vehicle, sterile PBS (batch n° 943548), was purchased from Eurobio Ingen (Les Ulis, France). Reference substances DMSO was prepared fresh on the day of administration at a final concentration of 50%. Appropriate volume was dissolved in vehicle at room temperature. DMSO was purchased from Sigma-Aldrich (Saint- Quentin Fallavier, France; batch n° RNBH3467). Ready to use Ialuril (batch n° 170501) was purchased from IBSA via Pharmaclic (Gosselies, Belgium). Treatment Experimental groups Seven (7) experimental groups were included as described in table 3. Table 3 – Experimental groups Pharmacological treatments Prior to the experiments, animals were randomly assigned to treatment groups. Randomization was designed to have at least one animal of each group on each experimental day and to assign a different position in the von Frey chamber for animals of the same group. In preparation for light pressure filling of the bladder with a solution, a polyethylene catheter (0.76 and 1.22 mm of internal and outer diameters, respectively) was inserted into the bladder through the urinary meatus. Test (Dysport) and reference substances (DMSO and laluril) and   vehicle (500 μL/rat) were administered into the bladder via a syringe which was connected to the catheter. Treatment was left in place for 30 min. Rats were maintained under isoflurane anesthesia (2 - 2.5%) during the whole procedure. After bladder filling, a gentle massage of the lower abdomen was performed to empty the bladder. Results Nociceptive scores Dysport treatment led to a significant decrease in nociceptive scores at D10 and at D12 with all the doses tested (10 U, 20 U and 30 U) when compared to CYP-injected rats treated with vehicle (see Figure 6). Nociceptive threshold Following CYP-injection, the nociceptive threshold of CYP-injected rats decreased at D7 when compared to D0 (see Figure 7A), indicating that chronic cystitis was induced and rats had a lower threshold in which pain was perceived. The nociceptive threshold was increased in CYP- injected rats after Dysport treatment at D10 and D12 when compared to CYP-injected rats treated with vehicle alone (see Figure 7B and Figure 7C). At D10, Dysport achieved the statistical significance level at the dose of 20 U/rat (see Figure 7B) whereas all tested doses reached the significance at D12 (see Figure 7C). CYP-injected rats treated with Dysport showed an increased nociceptive threshold compared to CYP-injected rats treated with DMSO or laluril, indicating that Dysport can effectively lower pain in CYP-treated animals. Chronic allodynia (AUC 1-6g) Following CYP-injection, an increase in AUC 1-6g was observed at D7 in CYP-injected rats when compared to saline treated rats (see Figure 8A) and D0. Following Dysport treatment, AUC 1-6g decreased at D10 (see Figure 8B) and D12 (see Figure 8C) for all doses tested when compared to CYP-injected rats treated with saline. CYP-injected rats treated with Dysport showed a greater decrease in AUC 1-6g when compared to CYP-injected rats treated with DMSO or laluril. These results suggest that the administration of Dysport can reduce pain perception associated with allodynia in CYP-treated animals. Chronic hyperalgesia (AUC 6-26g) Following CYP-injection, an increase in AUC 6-26g was observed at D7 when compared to saline treated rats (see Figure 9A). Following Dysport treatment, AUC 6-26g decreased at D10   (see Figure 9B) and D12 (see Figure 9C) for all doses tested when compared to CYP-injected rats treated with saline. CYP-injected rats treated with Dysport showed a greater decrease in AUC 6-26g when compared to CYP-injected rats treated with DMSO or laluril. These results suggest that Dysport can reduce pain perception associated with hyperalgesia in CYP-treated animals. EXAMPLE 2 A physician assesses a patient suffering from BPS, particularly IC, for their state of condition and performs a series of steps before administering a solution comprising a clostridial neurotoxin as treatment. Specifically, the urothelium of the patient’s bladder is assessed for its state of deterioration to determine the administration dosage of a clostridial neurotoxin in the form of a solution. The assessment by the physician identifies that the urothelium of the patient is severely damaged. The patient’s threshold volume of liquid that triggers micturition is then determined by either cystometry, uroflowmetry or by a voiding diary to determine the volume (in mls) of the solution comprising a clostridial neurotoxin to administer. The threshold volume is identified as 250 ml by cystometry. As the patient’s urothelium is severely damaged, the physician prepares a solution comprising a clostridial neurotoxin at a dose of 53,800 pg per 500 ml. The physician prepares thesolution at a total volume of 225 ml . The physician places a catheter into the patient’s bladder and infuses the solution into the bladder. The solution is then retained in the bladder for 1 hour. The patient is then asked to micturate, and the bladder is then rinsed with saline to remove any residual clostridial neurotoxin. EXAMPLE 3 A physician assesses a patient suffering from BPS, particularly IC, for their state of condition and performs a series of steps before administering a solution comprising a clostridial neurotoxin as treatment. Specifically, the urothelium of the patient’s bladder is assessed for its state of deterioration to determine the administration dosage of a clostridial neurotoxin in the form of a solution. The assessment by the physician identifies that the urothelium of the patient is mildly damaged, with some areas of tissue remaining intact. The patient’s threshold volume of liquid that triggers micturition is then determined by either cystometry, uroflowmetry or by a voiding diary to determine the volume (in mls) of a solution   comprising a clostridial neurotoxin to administer. The threshold volume is identified as 275 ml by a voiding diary. As the patient’s urothelium is mildly damaged, the physician prepares a solution comprising a clostridial neurotoxin at a dose of 161,400 pg per 500 ml. The physician prepares the solution at a total volume of 250 ml. The physician places a catheter into the patient’s bladder, connects the the catheter and infuses the solution into the bladder which is then retained in the bladder for 1 hour. The patient is then asked to micturate and the bladder is then rinsed with saline to remove any residual clostridial neurotoxin. All publications mentioned in the above specification are herein incorporated by reference. Various modifications and variations of the described methods and system of the present invention will be apparent to those skilled in the art without departing from the scope and spirit of the present invention. Although the present invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in biochemistry and biotechnology or related fields are intended to be within the scope of the following claims. EXAMPLE 4 Suppression of bladder mechanosensitivity by BoNT/A in an ex vivo mouse model These studies were performed using adult C57BL/6J mice between 8 and 12 weeks old (Charles River Laboratories, Margate, Kent). On the day of the experiment, mice were delivered and sacrificed using a rising concentration of CO2 in accordance with Schedule 1 of the Animals (Scientific Procedures) Act 1986. Experiments performed were in accordance with ethical approval obtained from the UCLan Animal Welfare and Ethics Review Board (AWERB) (reference RE/16/11). Ex vivo bladder electrophysiology Following CO ₂ asphyxiation, the fur on the back of the animal was removed along with the two hind limbs and tail. An incision was made on the abdomen to remove the intestine, and the spinal cord was cut at the L2 level above the kidneys. The whole pelvic region of the mouse was placed into an organ bath continuously perfused with carbogenated (95% O2 / 5% CO2) Krebs buffer (composition, in mM: NaCl 118.4, NaHCO ₃ 24.9, CaCl ₂ 1.9, MgSO ₄ 1.2, KH ₂ PO ₄   1.2, glucose 11.7; all acquired from Sigma-Aldrich) which was kept at a temperature of ~35°C to prevent tissue degradation. Once in the organ bath, the tissue was further dissected under a microscope. The ureters were tied with silk suture (Fisher-Scientific) to stop potential backflow during distension. The pubic symphysis was cut on the left and right sides and removed to expose the underlying urethra. The urethra was cut, and a catheter attached to a syringe pump (New Era Pump Systems, NE- 1000) was inserted and tied with suture to prevent leakage. The syringe contained phosphate buffer saline (PBS; Gibco), and the bladder was filled until a certain point where a syringe needle (BD microlance) could be inserted and pierced through the bladder dome without damaging the sensory nerves in the trigone. A double-lumen catheter was then inserted into the hole of the dome and tied with suture. One catheter was attached to a pressure transducer (NL108T2 Digitimer) to monitor intravesical pressure, and another was attached to a tap to allow filling and emptying of the bladder. A nerve bundle containing pelvic and hypogastric nerves was inserted into a glass electrode to facilitate capture of afferent nerve responses to bladder stimulation. Once catheterized, the bladder was distended to make sure it was a closed system, as failure to reach this pressure would indicate a leak. The pelvic and hypogastric nerves emerging from the bladder base were dissected into long nerve bundles and inserted into a glass suction electrode (VWR) attached to a Neurolog headstage (NL100AK). The headstage was connected to an AC pre-amp (NL104) to amplify the signal (10000x), filtered by a pass band filter (NL125) and the 50-60Hz electrical noise was removed by a Humbug (Quest Scientific). The signal was then passed through a 1401 Data Acquisition Interface (Cambridge Electronic Design) and recorded on a computer via Spike2 software (v10.08; Cambridge Electronic Design). Multi-unit afferent activity was quantified using a Spike processor (D130; Digitimer), which counted the number of field potentials passing a threshold set at the beginning of the experiment at twice the baseline noise level. The setup of the preparation is shown in Figure 10. Experimental protocols In the ex vivo bladder electrophysiological recordings, the bladder was stimulated through mechanical (distension) means, and the neuronal responses captured to characterise the effect of the stimulation parameters on afferent nerve activity.   Statistics All data pertaining to the ex vivo bladder electrophysiology assay were captured using Spike2 software (v10.08), including multi-unit nerve firing and intravesical pressure. Responses at 30, 60 and 90 minutes were normalised to the third reproducible control distension at the start of the experiment. Area under the curve was determined from this normalised data. N refers to number of animals, and all data are presented as mean +/- SEM. Statistical tests performed include T-tests, one-way ANOVA and two-way ANOVA using GraphPad Prism v8.0.1. Responses from all preparations were kept in the final analysis, assuming the experiment ran with no issues such as equipment failure, tissue failing to fill, the data was included. The specific methods of data extraction and analysis are described in detail below. Distension By closing the tap and turning on the syringe pump to fill at a speed of 150µL/min, the bladder slowly distended. The tap was opened to allow emptying, which caused the pressure to drop immediately. As the bladder filled, the activation of nerve fibres sensitive to mechanical stretch of the bladder wall was captured and visualised as field potentials on Spike2. Distensions were continued until three reproducible responses were reached concurrently. Once this was achieved, the experiment was started. All ramp distensions were performed 10 minutes apart, and each preparation was allowed to stabilise for at least 30 minutes before recording started. Bladder compliance Compliance is a measure of the pressure-volume relationship during bladder filling, or the ability of the bladder wall to accommodate increasing volumes. Volume (µL) = rate (µl/min-1) x time This equation was used to calculate the pressure volume relationship of the bladder using the rate of filling programmed on the intravesical pump. Changes in bladder compliance was also plotted as percentage change as compared to the control distension at the beginning of the experiment. Intraluminal application of BoNT/A The ex vivo bladder electrophysiology assay exhibited reproducibility over 120 minutes, as the response profile of the distension performed 90 minutes into the experiment was like that of the control distension at the beginning.   A syringe filled with a BoNT/A containing solution was connected to the syringe pump and the bladder was distended three times. This was to ensure uptake of BoNT/A across the urothelium. After this, the syringe was replaced with one containing PBS and distensions continued for 90 minutes to assess the effect of BoNT on bladder physiology. From a safety perspective, any BoNT/A present within intraluminal fluid was deactivated using Presept (Advanced Sterilization Products) as it came out of the dome catheter. Preliminary experiments revealed the BoNT/A concentration to provide robust, reproducible responses to be 100U/ml. The total toxin amount was calculated to be 3.6pM, this being the chosen amount of toxin employee for serotype comparative purposes. Results Intravesical application of 100U/ml Dysport led to a significant reduction in distension induced afferent firing over the 90-minute protocol (Figure 11; n = 9; p<0.0001). Bladder compliance increased following BoNT/A treatment (Figure 11; n = 9; p=0.0003). EXAMPLE 5 Suppression of bladder mechanosensitivity by BoNT/B in an ex vivo mouse model Following the same protocol as described in Example 4, distensions were performed until the distension-induced nerve responses were reproducible. Following three reproducible distensions using PBS, BoNT/B was applied intravesically using a syringe pump, the bladder was distended three times at a speed of 150 µL/min after which distensions were continued with PBS for nine distensions 10 minutes apart. As shown in Figure 12, BoNT/B reduced afferent firing in response to distension over time. This was found to be significant in the analysis (p <0.0001; n = 6). BoNT/B appeared to significantly increase the pressure-volume relationship of the bladder, which is taken as a measure of bladder compliance (p<0.0001). BoNT/B was found to significantly inhibit distension induced responses, as by 90 minutes following intravesical BoNT/B treatment, 52.3% (+/- 19.8%) of afferent firing remained. When compared to the inhibitory effect induced by BoNT/A, BoNT/B appeared to attenuate distension induced afferent firing to a greater degree.   EXAMPLE 6 Suppression of bladder mechanosensitivity by BoNT/E in an ex vivo mouse model Following the same protocol as described in Example 4, the effect of BoNT/E on bladder mechanosensitivity was investigated. As shown in Figure 13, distension-induced afferent firing was significantly reduced by BoNT/E (p<0.0001; n = 5). Bladder compliance was significantly increased following BoNT/E treatment. When compared to the effect of BoNT/A on bladder mechanosensitivity, BoNT/E demonstrated even more potent inhibition than was observed with BoNT/B.