Fig. 5

Summary of therapeutic strategies based on gene therapy for failing hearts. Early attempts were plasmid and adenovirus based. These reagents are usually locally delivered by intracoronary infusion or intramyocardial injection. The overexpressed genes encode secretory protein related to angiogenesis and tissue repair. In one trial, the putative protective adenylyl cyclase type 6 (AC6) was overexpressed. Recent gene therapy trials adopt adeno-associated virus (AAV). A series of clinical trials are designed to overexpress sarco/endoplasmic reticulum Ca²⁺-ATPase 2a (SERCA2a) in cardiomyocytes to improve Ca²⁺ handling in heart failure. Modified RNAs represent a novel approach to target specific genes. It’s normally systemically delivered. Although there hasn’t been any clinical trial testing RNA therapy for failing heart, preclinical studies using antisense oligonucleotide (ASO) against phospholamban (PLN) showed promising results. AAV: Adeno-associated virus; ASO: antisense oligonucleotide; FGF4: fibroblast growth factor 4; VEGF: vascular endothelial growth factor; SDF-1: stromal cell derived factor-1; SERCA: sarco/endoplasmic reticulum Ca2+-ATPase; PLN: phospholamban; AC6: Adenylyl cyclase type 6