Title:
COMBINATORIAL ADENINE AND CYTOSINE DNA BASE EDITORS
Document Type and Number:
WIPO Patent Application WO/2021/042062
Kind Code:
A3
Abstract:
Engineered bifunctional adenine and cytosine base editor (BACE) variants that enable expanded amino acid modifications and methods of using the same. Described herein are fusion proteins containing adenosine deaminases, cytidine deaminases, catalytically impaired CRISPR-Cas proteins (e.g., Cas9, CasX or Casl2 nucleases), linkers, nuclear localization signals (NLSs) and uracil-n-glycosylase inhibitors (UGIs) that enable the CRISPR-guided programmable introduction of simultaneous A-to-G (T-to-C) and C-to-T (G-to-A) substitutions in DNA.
Inventors:
JOUNG J KEITH (US)
ZHOU RONGHAO (US)
GRUNEWALD JULIAN (US)
ZHOU RONGHAO (US)
GRUNEWALD JULIAN (US)
Application Number:
PCT/US2020/048825
Publication Date:
April 08, 2021
Filing Date:
August 31, 2020
Export Citation:
Assignee:
JOUNG J KEITH (US)
ZHOU RONGHAO (US)
GRUNEWALD JULIAN (US)
ZHOU RONGHAO (US)
GRUNEWALD JULIAN (US)
International Classes:
C12N9/16; C07K19/00; C12N9/22; C12N15/11; C12N15/55; C12N15/62
Domestic Patent References:
| WO2020028823A1 | 2020-02-06 | |||
| WO2020163396A1 | 2020-08-13 |
Foreign References:
| US20180312828A1 | 2018-11-01 | |||
| US20180073012A1 | 2018-03-15 | |||
| US20190010481A1 | 2019-01-10 | |||
| US20190106687A1 | 2019-04-11 |
Other References:
GAUDELLI ET AL.: "Programmable base editing of A·T to G·C in genomic DNA without DNA cleavage", NATURE, vol. 551, 23 November 2017 (2017-11-23), pages 464 - 471, XP037336615
GRUNEWALD ET AL.: "A dual-deaminase CRISPR base editor enables concurrent adenine and cytosine editing", NATURE BIOTECHNOL, vol. 38, 1 June 2020 (2020-06-01), pages 861 - 864, XP037187544, DOI: 10.1038/s41587-020-0535-y
GRUNEWALD ET AL.: "CRISPR DNA base editors with reduced RNA off-target and self-editing activities", NAT BIOTECHNOL, vol. 37, no. 9, 2 September 2019 (2019-09-02), pages 1 - 19, XP036878180
GRUNEWALD ET AL.: "A dual-deaminase CRISPR base editor enables concurrent adenine and cytosine editing", NATURE BIOTECHNOL, vol. 38, 1 June 2020 (2020-06-01), pages 861 - 864, XP037187544, DOI: 10.1038/s41587-020-0535-y
GRUNEWALD ET AL.: "CRISPR DNA base editors with reduced RNA off-target and self-editing activities", NAT BIOTECHNOL, vol. 37, no. 9, 2 September 2019 (2019-09-02), pages 1 - 19, XP036878180
Attorney, Agent or Firm:
DEYOUNG, Janice Kugler et al. (US)
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