Cell and gene based methods to improve cardiac function

US9868937B2 · kind B2 · utility

Assignee

• University of Washington · US

Inventors

• Michael REGNIER · Seattle, US
• Michael Laflamme · Seattle, US
• Charles E. MURRY · Seattle, US
• F. Steven Korte · Port Orchard, US
• Scott Lundy · Shoreline, US
• Stephen D. Hauschka · Seattle, US
• Jeffrey S. Chamberlain · Ann Arbor, US
• Guy L. ODOM · Seattle, US

Key dates

• Filing date: May 29, 2012
• Grant date: Jan 16, 2018
• Expiry date: Nov 24, 2034

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Y117/04001
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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.