Selection of an Efficient AAV Vector for Robust CNS Transgene Expression

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 r...

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Detalles Bibliográficos
Autores principales: Hanlon, Killian S., Meltzer, Jonah C., Buzhdygan, Tetyana, Cheng, Ming J., Sena-Esteves, Miguel, Bennett, Rachel E., Sullivan, Timothy P., Razmpour, Roshanak, Gong, Yi, Ng, Carrie, Nammour, Josette, Maiz, Daniela, Dujardin, Simon, Ramirez, Servio H., Hudry, Eloise, Maguire, Casey A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881693/
https://www.ncbi.nlm.nih.gov/pubmed/31788496
http://dx.doi.org/10.1016/j.omtm.2019.10.007
Descripción
Sumario: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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