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• W3198709600 abstract "Adeno-associated virus (AAV) is a promising gene therapy vector, but questions remain regarding mechanisms of basic viral functions. We previously showed that a serine/threonine (S/T) triplet motif and its flanking residues, located in the overlapping N-terminus of VP1/VP2 and highly conserved across most AAV serotypes, are critical for viral transcript production in vitro. Here we generate a panel of S/T triplet mutants in AAV serotypes 2, 4, and 9 and characterize their behaviors in vitro and in vivo using next generation sequencing. We show that S/T triplet mutations can significantly hinder some stages of transduction in a serotype-dependent manner in vitro. Interestingly, these defects are largely overcome in C57BL/6 mice, with only one mutant displaying altered behavior in vivo. Taken together, our results identify a short N-terminal capsid motif with diverse roles across several AAV serotypes which better informs engineering efforts to improve AAV as a vector for gene therapy." @default.
• W3198709600 created "2021-09-13" @default.
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• W3198709600 date "2021-11-01" @default.
• W3198709600 modified "2023-10-14" @default.
• W3198709600 title "N-terminal serine/threonine motif has diverse and important effects on behavior of multiple AAV serotypes" @default.
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• W3198709600 doi "https://doi.org/10.1016/j.virol.2021.08.010" @default.
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