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Selection of an Efficient AAV Vector for Robust CNS Transgene Expression

Mol Ther Methods Clin Dev.. 2019;

Hanlon KS1,2,3, Meltzer JC3,4, Buzhdygan T5,6,7, Cheng MJ2,3, Sena-Esteves M8, Bennett RE3,4, Sullivan TP5,6,7, Razmpour R5,6,7, Gong Y2,3, Ng C2,3, Nammour J2,3, Maiz D3,4, Dujardin S3,4, Ramirez SH5,6,7, Hudry E3,4, Maguire CA2,3.

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Mutant Libraries	… Deverman et al. 12 ). Both the mutant Cre cDNA (Cre mut ) flanked by KpnI and SalI<br> restriction sites and the p41-CAP9(del)-poly(A) fragment were synthesized by <b>GenScript</b><br> and cloned into a puC57 backbone. We constructed first …	Get A Quote

摘要

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-independe... More