Heart failure gene therapy: the path to clinical practice

Circ Res. 2013 Aug 30;113(6):792-809. doi: 10.1161/CIRCRESAHA.113.300269.


Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses formulations of DNA and RNA, whose products determine the therapeutic classification through their biological actions. Among resident cardiac cells, cardiomyocytes have been the therapeutic target of numerous attempts to regenerate systolic and diastolic performance, to reverse remodeling and restore electric stability and metabolism. Although the concept to intervene directly within the genetic and molecular foundation of cardiac cells is simple and elegant, the path to clinical reality has been arduous because of the challenge on delivery technologies and vectors, expression regulation, and complex mechanisms of action of therapeutic gene products. Nonetheless, since the first demonstration of in vivo gene transfer into myocardium, there have been a series of advancements that have driven the evolution of heart failure gene therapy from an experimental tool to the threshold of becoming a viable clinical option. The objective of this review is to discuss the current state of the art in the field and point out inevitable innovations on which the future evolution of heart failure gene therapy into an effective and safe clinical treatment relies.

Keywords: cardiac; clinical translation; gene therapy; heart failure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenylyl Cyclases / genetics
  • Animals
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Heart Failure / genetics
  • Heart Failure / therapy*
  • Humans
  • Receptors, Adrenergic, beta / genetics
  • S100 Proteins / genetics
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics


  • Receptors, Adrenergic, beta
  • S100 Proteins
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Adenylyl Cyclases
  • adenylyl cyclase 6