US 12,221,636 B2
Systems methods, and compositions for targeted nucleic acid editing
Feng Zhang, Cambridge, MA (US); Jonathan Gootenberg, Cambridge, MA (US); and Omar Abudayyeh, Cambridge, MA (US)
Assigned to THE BROAD INSTITUTE, INC., Cambridge, MA (US); MASSACHUSETTS INSTITUTE OF TECHNOLOGY, Cambridge, MA (US); and PRESIDENT AND FELLOWS OF HARVARD COLLAGE, Cambridge, MA (US)
Appl. No. 16/650,480
Filed by THE BROAD INSTITUTE, INC., Cambridge, MA (US); MASSACHUSETTS INSTITUTE OF TECHNOLOGY, Cambridge, MA (US); and PRESIDENT AND FELLOWS OF HARVARD COLLEGE, Cambridge, MA (US)
PCT Filed Oct. 4, 2018, PCT No. PCT/US2018/054469
§ 371(c)(1), (2) Date Mar. 25, 2020,
PCT Pub. No. WO2019/071048, PCT Pub. Date Apr. 11, 2019.
Claims priority of provisional application 62/568,313, filed on Oct. 4, 2017.
Prior Publication US 2021/0009972 A1, Jan. 14, 2021
Int. Cl. C12N 9/22 (2006.01); C12N 9/78 (2006.01); C12N 15/113 (2010.01); C12N 15/86 (2006.01)
CPC C12N 9/22 (2013.01) [C12N 9/78 (2013.01); C12N 15/113 (2013.01); C12N 15/86 (2013.01); C12Y 305/04004 (2013.01); C12Y 305/04005 (2013.01); C12N 2310/20 (2017.05); C12N 2800/80 (2013.01)] 37 Claims
 
1. An engineered composition for site directed base editing comprising:
a) a targeting domain; and
b) an adenosine deaminase or catalytic domain thereof, wherein the adenosine deaminase is modified to convert activity to a cytidine deaminase, wherein the adenosine deaminase or catalytic domain thereof comprises one or more mutations selected from P462A, N597I, or both of a human ADAR2 or mutations corresponding thereto in a homologue, ortholog, or variant thereof.