REGNIER MICHAEL,LAFLAMME MICHAEL,MURRY CHARLES,KORTE F STEVEN,LUNDY SCOTT,HAUSCHKA STEPHEN DENISON,CHAMBERLAIN JEFFREY S
申请号：
IN10634/DELNP/2013
公开号：
IN2013DN10634A
申请日:
2013.12.10
申请国别(地区):
IN
年份:
2016
代理人:
摘要：
Compositions and methods for improving cardiac function, myocardial contractility and relaxation in a mammal are provided. Cardiomyocytes transfected with one or more expression vectors comprising a ribonucleotide reductase subunit Rl-encoding nucleic acid sequence and a ribonucleotide reductase subunit R2-encoding nucleic acid sequence operably linked to a promoter are grafted to a mammalian myocardium. Also provided are compositions and methods for delivering dATP to a myocardium through grafting of donor cells overexpressing R1 and R2. dATP is thereby produced in situ and delivered through gap junctions established between donor cells and host cardiomyocytes. Alternatively, viral vector(s) having the Rl and R2-encoding construct(s) are administered to the mammal directly. Improvement of cardiac function can also be effected by administration of vectors comprising a nucleic acid sequence encoding a L48Q, 61 Q, or L57Q cTnC variant.
