Surgical Methods for Cardiac Gene Delivery in Large Animals

Michael G. Katz, Yoav Hadas, Adam S. Vincek, Nataly Shtraizent, Hylton P. Gordon, Peter Pastuszko, Eric Schadt, Efrat Eliyahu

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


This chapter describes main strategies of surgical gene delivery in large animals. Existing methods of cardiac gene transfer can be classified by the site of injection, interventional approach, and type of cardiac circulation at the time of transfer. Randomized clinical trials have suggested that the therapeutic benefits of gene therapy are not as substantial as expected from animal studies. This discordance in results is largely due to gene delivery methods that may be effective in small animals but are not scalable to larger species and, therefore, cannot transduce a sufficient fraction of myocytes to establish long-term clinical efficacy. Ideally, an optimized gene transfer should incorporate the following: a closed-loop recirculation for extended transgene residence time; vector washout form the vascular system after transfer to prevent collateral expression; use of methods to increase myocardial transcapillary gradient for viral particles for a better transduction, probably retrograde route of gene delivery through the coronary venous system; and myocardial ischemic preconditioning.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Number of pages15
StatePublished - 2022

Publication series

NameMethods in Molecular Biology
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029


  • Cardiac gene therapy
  • Cardiopulmonary bypass
  • Cardiovascular diseases
  • Gene delivery
  • Intramyocardial administration


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