Percutaneous Transendocardial Delivery of Self-complementary Adeno-associated Virus 6 Achieves Global Cardiac Gene Transfer in Canines
Authors
Bish, Lawrence T.Sleeper, Meg M.
Brainard, Benjamin
Cole, Stephen
Russell, Nicholas
Withnall, Elanor
Arndt, Jason
Reynolds, Caryn
Davison, Ellen
Sanmiguel, Julio
Wu, Di
Gao, Guangping
Wilson, James M.
Lee Sweeney, H
Document Type
Journal ArticlePublication Date
2008-12-01
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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.Source
Mol Ther. 2008 Dec;16(12):1953-1959. doi: 10.1038/mt.2008.202. Epub 2016 Dec 8. Link to article on publisher's siteDOI
10.1038/mt.2008.202Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40244PubMed ID
28189009Related Resources
Link to Article in PubMedDistribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1038/mt.2008.202
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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-nd/4.0/