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• W2047667011 abstract "A detailed comparison of recombinant adeno-associated viral (rAAV) vectors of serotypes 2, 5, and 8 was performed in mice and nonhuman primates. Differences within the capsid proteins and viral terminal repeats of rAAV-2 and -5 did not significantly influence their ability to transduce murine liver. However, vectors pseudotyped with AAV-8 capsid (rAAV-2/8) mediated transgene expression more rapidly and from lower doses than possible with rAAV-2 and -5, although expression declined from peak values in a distinct dose-dependent manner prior to reaching steady-state levels. Nevertheless, at all time points and vector doses, rAAV-2/8 transgene levels were 17- to 84-fold higher than with rAAV-2 or -5 due to a more rapid conversion of the single-stranded genome to transcriptionally active stable duplex DNA. In nonhuman primates, liver-targeted administration of rAAV-5 and rAAV-2/8 vectors established therapeutic levels of transgene expression. The importance of preexisting serotype immunity was highlighted by the inability to achieve successful transduction in the presence of serotype-specific antibodies, although this impediment was successfully avoided through the use of alternative serotypes. In summary, serotype-specific differences in transduction biology and the appreciation of preexisting immunity will likely influence the selection of the rAAV serotype for future clinical trials." @default.
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• W2047667011 date "2005-06-01" @default.
• W2047667011 modified "2023-10-17" @default.
• W2047667011 title "Comparison of the ability of adeno-associated viral vectors pseudotyped with serotype 2, 5, and 8 capsid proteins to mediate efficient transduction of the liver in murine and nonhuman primate models" @default.
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• W2047667011 doi "https://doi.org/10.1016/j.ymthe.2004.12.022" @default.
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