	US 12,404,522 B2
	Disrupting the LINC complex for treating laminopathy
Colin Lawson Stewart, Singapore (SG); Jinfen Chai, Singapore (SG); Yin Loon Lee, Singapore (SG); and Brian Edmund Burke, Singapore (SG)
Assigned to Agency for Science, Technology and Research, Singapore (SG)
Appl. No. 16/962,877
Filed by Agency for Science, Technology and Research, Singapore (SG)
PCT Filed Jan. 18, 2019, PCT No. PCT/SG2019/050033 § 371(c)(1), (2) Date Jul. 17, 2020, PCT Pub. No. WO2019/143300, PCT Pub. Date Jul. 25, 2019.
Application 16/962,877 is a continuation in part of application No. PCT/SG19/50033, filed on Jan. 18, 2019.
Claims priority of application No. 10201800530Q (SG), filed on Jan. 19, 2018.
Prior Publication US 2020/0347408 A1, Nov. 5, 2020
Int. Cl. C12N 15/86 (2006.01); A61P 9/00 (2006.01); C12N 7/00 (2006.01); G01N 33/50 (2006.01)

CPC C12N 15/86 (2013.01) [A61P 9/00 (2018.01); C12N 7/00 (2013.01); G01N 33/502 (2013.01); C12N 2750/14143 (2013.01)]

13 Claims

1. A method of treating a laminopathy in a subject in need thereof, wherein the laminopathy is a disease caused by a mutation in the Lamin A (LMNA) gene, the method comprising administering to the subject an effective amount of an adeno-associated virus (AAV) expression vector operably linked to a transgene; wherein the transgene comprises a nucleic acid sequence encoding a dominant negative Sun domain containing protein; wherein the AAV expression vector comprises a cardiac-or cardiomyocyte-specific promoter; wherein the AAV expression vector is administered intravascularly, wherein expression of the dominant negative Sun domain containing protein disrupts the protein-protein interactions of the Linker of Nucleoskeleton and Cyotoskeleton (LINC) complex, which uncouples the nucleus from its linkage to the cytoskeleton, resulting in treatment of the laminopathy.