Gene Therapy Approaches to Biological Pacemakers.

• Type of Material: Article
• Authors: Melad Farraha, The University of Sydney; Saurabh Kumar, Westmead Hospital; James Chong, The University of Sydney; Hee Cheol Cho, Emory University; Eddy Kizana, The University of Sydney
• Language: English
• Date: 2018-10-19
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2018 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/jcdd5040050
• Title of Journal or Parent Work: Journal of Cardiovascular Development and Disease
• ISSN: 2308-3425
• Volume: 5
• Issue: 4
• Grant/Funding Information: MF was supported by the MyWestmead Early Career Research Scholarship and Arab Bank Postgraduate Research Scholarship from the Westmead Medical Research Foundation.; Our work was supported by a National Health and Medical Research Council of Australia Project Grant (APP1128864) to EK, Future Leader Fellowship (ID 100463) from the National Heart Foundation of Australia (JJHC) and a Sydney Medical School Foundation Fellowship (JJHC).
• Keywords: atrioventricular node; heart; viral vector; bradycardia; pacemaker; sinoatrial node; gene therapy
• Research Categories: Engineering, Biomedical; Biology, Genetics

Abstract

Bradycardia arising from pacemaker dysfunction can be debilitating and life threatening. Electronic pacemakers serve as effective treatment options for pacemaker dysfunction. They however present their own limitations and complications. This has motivated research into discovering more effective and innovative ways to treat pacemaker dysfunction. Gene therapy is being explored for its potential to treat various cardiac conditions including cardiac arrhythmias. Gene transfer vectors with increasing transduction efficiency and biosafety have been developed and trialed for cardiovascular disease treatment. With an improved understanding of the molecular mechanisms driving pacemaker development, several gene therapy targets have been identified to generate the phenotypic changes required to correct pacemaker dysfunction. This review will discuss the gene therapy vectors in use today along with methods for their delivery. Furthermore, it will evaluate several gene therapy strategies attempting to restore biological pacing, having the potential to emerge as viable therapies for pacemaker dysfunction.