Department of Molecular Genetics and Microbiology; Gene Therapy Center
Cardiology | Cellular and Molecular Physiology | Genetics and Genomics | Therapeutics
Achieving efficient cardiac gene transfer in a large animal model has proven to be technically challenging. Previous strategies have used cardiopulmonary bypass or dual catheterization with the aid of vasodilators to deliver vectors, such as adenovirus, adeno-associated virus (AAV), or plasmid DNA. Although single-stranded AAV (ssAAV) vectors have shown the greatest promise, they suffer from delayed expression, which might be circumvented using self-complementary vectors. We sought to optimize cardiac gene transfer using a percutaneous transendocardial injection catheter to deliver adeno-associated viral vectors to the canine myocardium. Four vectors were evaluated-ssAAV9, self-complementary AAV9 (scAAV9), scAAV8, scAAV6-so that comparison could be made between single-stranded and self-complementary vectors as well as among serotypes 9, 8, and 6. We demonstrate that scAAV is superior to ssAAV and that AAV 6 is superior to the other serotypes evaluated. Biodistribution studies revealed that vector genome copies were 15-4,000 times more abundant in the heart than in any other organ for scAAV6. Percutaneous transendocardial injection of scAAV6 is a safe, effective method to achieve efficient cardiac gene transfer.
DOI of Published Version
Mol Ther. 2008 Dec;16(12):1953-1959. doi: 10.1038/mt.2008.202. Epub 2016 Dec 8. Link to article on publisher's site
Molecular therapy : the journal of the American Society of Gene Therapy
Bish LT, Sleeper MM, Brainard B, Cole S, Russell N, Withnall E, Arndt J, Reynolds C, Davison E, Sanmiguel J, Wu D, Gao G, Wilson JM, Lee Sweeney H. (2008). Percutaneous Transendocardial Delivery of Self-complementary Adeno-associated Virus 6 Achieves Global Cardiac Gene Transfer in Canines. Open Access Articles. https://doi.org/10.1038/mt.2008.202. Retrieved from https://escholarship.umassmed.edu/oapubs/3038
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.