Selection of an Efficient AAV Vector for Robust CNS Transgene Expression
Hanlon, Killian S. Sena-Esteves, Miguel Hudry, Eloise Maguire, Casey A.
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Abstract
Adeno-associated virus (AAV) capsid libraries have generated improved transgene delivery vectors. We designed an AAV library construct, iTransduce, that combines a peptide library on the AAV9 capsid with a Cre cassette to enable sensitive detection of transgene expression. After only two selection rounds of the library delivered intravenously in transgenic mice carrying a Cre-inducible fluorescent protein, we flow sorted fluorescent cells from brain, and DNA sequencing revealed two dominant capsids. One of the capsids, termed AAV-F, mediated transgene expression in the brain cortex more than 65-fold (astrocytes) and 171-fold (neurons) higher than the parental AAV9. High transduction efficiency was sex-independent and sustained in two mouse strains (C57BL/6 and BALB/c), making it a highly useful capsid for CNS transduction of mice. Future work in large animal models will test the translation potential of AAV-F.
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Mol Ther Methods Clin Dev. 2019 Oct 23;15:320-332. doi: 10.1016/j.omtm.2019.10.007. eCollection 2019 Dec 13. Link to article on publisher's site
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Full author list omitted for brevity. For the full list of authors, see article.