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AssigneeUniversity of Washington
InventorsMichael Regnier, Michael Laflamme, Charles Murry, F. Steven Korte, Scott Lundy, Stephen Denison Hauschka, Jeffrey S. Chamberlain, Guy Odom
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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 R1-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 R1 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.
A pharmaceutical composition comprising a first viral vector comprising a first nucleic acid sequence encoding ribonucleotide reductase subunit R1 and a second viral vector comprising a second nucleic acid sequence encoding ribonucleotide reductase subunit R2, said first nucleic acid sequence and second nucleic acid sequence being operably linked to a cardiac-specific promoter, wherein said cardiac-specific promoter comprises the nucleic acid sequence SEQ ID NO:
A pharmaceutical composition comprising cardiomyocytes containing a first expression vector comprising a first nucleic acid sequence encoding ribonucleotide reductase subunit R1 and a second expression vector comprising a second nucleic acid sequence encoding ribonucleotide reductase subunit R2, said first nucleic acid sequence and second nucleic acid sequence being operably linked to a promoter that induces overexpression of R1 and R2, wherein said promoter that induces overexpression of R1 and R2 comprises the nucleic acid sequence SEQ ID NO:
Dependencies are inferred from the claim text.