Title:
A MULTIPLEXED RNA REGULATION PLATFORM FOR PRIMARY IMMUNE CELL ENGINEERING
Document Type and Number:
WIPO Patent Application WO/2024/044672
Kind Code:
A3
Abstract:
The present disclosure provides a versatile and multi-functional platform for transcriptome regulation using the RNA-guided, RNA-targeting activity of type VI-D CRISPR effectors with RNA-guided RNA endonuclease activity combined with guide arrays that express a plurality of guide RNAs. The system can be used to perform quantitative, reversible, and massively-multiplexed gene knockdown in primary human T cells and to perform multiplexed suppression of exhaustion-associated genes in T cells. The system can be used to enhance the anti-tumor activity of dysfunctional CAR T cells.
Inventors:
QI LEI S (US)
TIEU VICTOR (US)
MACKALL CRYSTAL L (US)
SOTILLO ELENA (US)
TIEU VICTOR (US)
MACKALL CRYSTAL L (US)
SOTILLO ELENA (US)
Application Number:
PCT/US2023/072798
Publication Date:
April 25, 2024
Filing Date:
August 24, 2023
Export Citation:
Assignee:
UNIV LELAND STANFORD JUNIOR (US)
International Classes:
C12N15/113; A61K39/00; C12N9/22
Domestic Patent References:
| WO2022020431A2 | 2022-01-27 | |||
| WO2022159402A1 | 2022-07-28 | |||
| WO2019040664A1 | 2019-02-28 | |||
| WO2019178422A1 | 2019-09-19 |
Other References:
SILVANA KONERMANN ET AL: "Transcriptome Engineering with RNA-Targeting Type VI-D CRISPR Effectors", CELL, vol. 173, no. 3, 19 April 2018 (2018-04-19), Amsterdam NL, pages 665 - 676, XP055529705, ISSN: 0092-8674, DOI: 10.1016/j.cell.2018.02.033
LIN MEI-WEI ET AL: "Enhancing the yield and activity of defucosylated antibody produced by CHO-K1 cells using Cas13d-mediated multiplex gene targeting", JOURNAL OF THE TAIWAN INSTITUTE OF CHEMICAL ENGINEERS, ELSEVIER, AMSTERDAM, NL, vol. 121, 10 April 2021 (2021-04-10), pages 38 - 47, XP086568708, ISSN: 1876-1070, [retrieved on 20210410], DOI: 10.1016/J.JTICE.2021.03.040
ZHANG KUN ET AL: "CRISPR/Cas13d-Mediated Microbial RNA Knockdown", FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, vol. 8, 30 July 2020 (2020-07-30), XP093041172, DOI: 10.3389/fbioe.2020.00856
STADTMAUER EDWARD A. ET AL: "CRISPR-engineered T cells in patients with refractory cancer", SCIENCE, vol. 367, no. 6481, 28 February 2020 (2020-02-28), US, XP055896641, ISSN: 0036-8075, DOI: 10.1126/science.aba7365
WEBBER BEAU R ET AL: "Highly efficient multiplex human T cell engineering without double-strand breaks using Cas9 base editors", NATURE COMMUNICATIONS, vol. 10, no. 1, 19 November 2019 (2019-11-19), UK, pages 5222, XP055834302, ISSN: 2041-1723, DOI: 10.1038/s41467-019-13007-6
LIN MEI-WEI ET AL: "Enhancing the yield and activity of defucosylated antibody produced by CHO-K1 cells using Cas13d-mediated multiplex gene targeting", JOURNAL OF THE TAIWAN INSTITUTE OF CHEMICAL ENGINEERS, ELSEVIER, AMSTERDAM, NL, vol. 121, 10 April 2021 (2021-04-10), pages 38 - 47, XP086568708, ISSN: 1876-1070, [retrieved on 20210410], DOI: 10.1016/J.JTICE.2021.03.040
ZHANG KUN ET AL: "CRISPR/Cas13d-Mediated Microbial RNA Knockdown", FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, vol. 8, 30 July 2020 (2020-07-30), XP093041172, DOI: 10.3389/fbioe.2020.00856
STADTMAUER EDWARD A. ET AL: "CRISPR-engineered T cells in patients with refractory cancer", SCIENCE, vol. 367, no. 6481, 28 February 2020 (2020-02-28), US, XP055896641, ISSN: 0036-8075, DOI: 10.1126/science.aba7365
WEBBER BEAU R ET AL: "Highly efficient multiplex human T cell engineering without double-strand breaks using Cas9 base editors", NATURE COMMUNICATIONS, vol. 10, no. 1, 19 November 2019 (2019-11-19), UK, pages 5222, XP055834302, ISSN: 2041-1723, DOI: 10.1038/s41467-019-13007-6
Attorney, Agent or Firm:
YAN, Lin et al. (US)
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