US 12,215,382 B2
Liver protective MARC variants and uses thereof
Sekar Kathiresan, Boston, MA (US); and Connor Emdin, Boston, MA (US)
Assigned to The General Hospital Corporation, Boston, MA (US)
Filed by THE GENERAL HOSPITAL CORPORATION, Boston, MA (US)
Filed on Mar. 2, 2020, as Appl. No. 16/807,125.
Claims priority of provisional application 62/812,881, filed on Mar. 1, 2019.
Prior Publication US 2021/0262022 A1, Aug. 26, 2021
Int. Cl. C12N 15/11 (2006.01); A61K 31/7088 (2006.01); A61K 31/713 (2006.01); A61K 45/06 (2006.01); C12Q 1/6858 (2018.01)
CPC C12Q 1/6858 (2013.01) [A61K 31/7088 (2013.01); A61K 31/713 (2013.01); A61K 45/06 (2013.01); C12Q 2600/158 (2013.01)] 12 Claims
 
1. A method of making a protective modification of a MARC1 gene in a subject comprising:
detecting a MARC1 protein variant or a MARC1 protein variant-encoding polynucleotide in the subject, wherein the MARC1 protein variant comprises alanine at a position in the MARC1 protein of the subject corresponding to position 165 of SEQ ID NO: 1; and
administering, to the subject thereof having the MARC1 protein variant or the MARC1 protein variant-encoding polynucleotide, a programmable nuclease-based system comprising a nuclease or a guide polynucleotide each configured to bind a target polynucleotide, wherein the target polynucleotide is the MARC1 protein variant-encoding polynucleotide, and
wherein the programmable nuclease-based system is configured to modify the MARC1 protein variant-encoding polynucleotide from the alanine at the position in the MARC1 protein of the subject corresponding to position 165 of SEQ ID NO: 1 to a threonine, thereby making a protective modification of the MARC1 gene in the subject.