US 12,029,795 B2
Base editing of PCSK9 and methods of using same for treatment of disease
Alexandra Chadwick, Somerville, MA (US); Kallanthottathil G. Rajeev, Wayland, MA (US); Ellen Rohde, Ashland, MA (US); Christopher Cheng, North Reading, MA (US); and Caroline Reiss, Somerville, MA (US)
Assigned to VERVE THERAPEUTICS, INC., Boston, MA (US)
Appl. No. 17/918,057
Filed by Verve Therapeutics, Inc., Boston, MA (US)
PCT Filed Apr. 9, 2021, PCT No. PCT/US2021/026732
§ 371(c)(1), (2) Date Oct. 10, 2022,
PCT Pub. No. WO2021/207712, PCT Pub. Date Oct. 14, 2021.
Claims priority of provisional application 63/136,087, filed on Jan. 11, 2021.
Claims priority of provisional application 63/045,032, filed on Jun. 26, 2020.
Claims priority of provisional application 63/045,033, filed on Jun. 26, 2020.
Claims priority of provisional application 63/007,803, filed on Apr. 9, 2020.
Claims priority of provisional application 63/007,797, filed on Apr. 9, 2020.
Prior Publication US 2023/0159926 A1, May 25, 2023
Int. Cl. C07H 21/04 (2006.01); A61K 9/127 (2006.01); A61K 31/7105 (2006.01); A61K 38/46 (2006.01); A61K 48/00 (2006.01); C07K 14/515 (2006.01); C12N 9/22 (2006.01); C12N 15/11 (2006.01); C12N 15/113 (2010.01); C12N 15/90 (2006.01)
CPC A61K 48/0066 (2013.01) [A61K 9/127 (2013.01); A61K 31/7105 (2013.01); A61K 38/465 (2013.01); C07K 14/515 (2013.01); C12N 9/22 (2013.01); C12N 15/11 (2013.01); C12N 15/113 (2013.01); C12N 15/907 (2013.01); C07K 2319/09 (2013.01); C07K 2319/80 (2013.01); C12N 2310/20 (2017.05); C12N 2310/315 (2013.01); C12N 2310/321 (2013.01); C12N 2310/331 (2013.01); C12N 2310/335 (2013.01); C12N 2310/344 (2013.01); C12N 2310/3521 (2013.01); C12N 2800/80 (2013.01)] 24 Claims
 
1. A composition for editing a gene target comprising:
(i) an mRNA encoding a base editor protein comprising a DNA binding domain and a deaminase, wherein the mRNA comprises a sequence having at least 95% sequence identity to SEQ ID NO: 2192, and
(ii) a guide RNA comprising a tracr sequence that serves as a binding scaffold for the base editor protein, and a spacer sequence that corresponds to a protospacer on a target gene;
wherein the target gene is PCSK9.