Cycle adenosine monophosphate-incompetent adenylyl cyclase and compositions and methods for treating heart failure and increasing cardiac function

A method for increasing cardiac function,

• thereby treating, ameliorating, or reversing the effects of a heart failure in an individual in need thereof,
• comprising
• administering via intracoronary injection a nucleic acid comprising a sequence encoding a mutated adenylyl cyclase type 6 (AC6mut) protein having a sequence comprising SEQ ID NO:13, in which an alanine (ala) replaces an aspartic acid (asp) at amino acid residue 426, rendering the AC6mut protein having reduced ability to catalyze the breakdown of ATP to cAMP, thus having reduced capacity to generate increased levels of cAMP,
• wherein the AC6mut protein is encoded by a nucleic acid operatively linked to a transcriptional regulatory sequence, which comprises a cytomegalovirus (CMV) promoter, an adenylyl cyclase (AC) gene promoter, or a myocyte cell-specific promoter,
• wherein the AC6mut protein-encoding nucleic acid is contained in an adenovirus vector,
• wherein the AC6mut protein when expressed causes an increase in ATP-dependent sarcoplasmic reticulum (SR) Ca++ uptake and release and a decrease in phospholamban (PLB) expression and function,
• thereby increasing cardiac function and treating, ameliorating, or reversing the effects of the heart failure.