Journal
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
Volume 15, Issue -, Pages 320-332Publisher
CELL PRESS
DOI: 10.1016/j.omtm.2019.10.007
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Funding
- NIH/NIDCD [R01DC017117-01A1]
- NIH/NIA [R00AG047336-05]
- NIH from the Eunice Kennedy Shriver National Institute of Child Health & Human Development [5R24HD00083]
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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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