Gene delivery methods in cardiac gene therapy

Abstract

Gene therapy for the treatment of heart failure is emerging as a multidisciplinary field demonstrating advances with respect to identifying key signaling pathways, modernized vector creation and delivery technologies. Although these discoveries offer significant progress, selecting optimal methods for the vector delivery remains a key component for efficient cardiac gene therapy to validate the targets in rodent models and to test clinically relevant ones in pre-clinical models. Although the goals of higher transduction efficiency and cardiac specificity can be achieved with several delivery methods, the invasiveness and patient safety remain unclear for clinical application. In this review, we discuss various features of the currently available vector delivery methods for cardiac gene therapy.

Long-Term Robust Myocardial Transduction of the Dog Heart from a Peripheral Vein by Adeno-Associated Virus Serotype-8

“…A number of complicated techniques have been developed to transduce the myocardium by direct injection (to the myocardium or ventricular cavity), pericardial injection, coronary perfusion, and aorta injection using a variety of viral and nonviral vectors (Ishikawa et al, 2011;Katz et al, 2011;Wasala et al, 2011). Some of these invasive cardiac gene delivery methods, such as percutaneous intracoronorary delivery, have begun to show promise in treating heart failure in human patients ( Jaski et al, 2009;Jessup et al, 2011).…”

Ultrasound-targeted cardiovascular gene therapy

“…11 Direct intramyocardial/intramuscular injections are limited in their effectiveness due to more focal transfection at injection sites, 12 whereas intracoronary/intra-arterial injections are hampered by rapid clearance of plasma DNases. 13 With an increased understanding of the biological effects of microbubble agents exposed to ultrasound, much scientifi c interest has focused on harnessing these bioeffects to develop non-invasive methods of gene and drug delivery.…”

Cardiac gene therapy: Recent advances and future directions

“…A layer of endothelial cells serves as another barrier in case of gene delivery specifically targeted to cardiac tissue. To bypass this barrier, techniques such as direct injection into the myocardium and local trans-endothelial delivery methods like retrofusion have been developed [43].…”