Selection of an Efficient AAV Vector for Robust CNS Transgene Expression
oleh: Killian S. Hanlon, Jonah C. Meltzer, Tetyana Buzhdygan, Ming J. Cheng, Miguel Sena-Esteves, Rachel E. Bennett, Timothy P. Sullivan, Roshanak Razmpour, Yi Gong, Carrie Ng, Josette Nammour, Daniela Maiz, Simon Dujardin, Servio H. Ramirez, Eloise Hudry, Casey A. Maguire
| Format: | Article |
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| Diterbitkan: | Elsevier 2019-12-01 |
Deskripsi
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. Keywords: adeno-associated virus vector, AAV vector, gene therapy, gene delivery, central nervous system, transduction efficiency, AAV capsid library