What question did this study set out to answer?

To compare the hepatic transduction efficiency, kinetics, and effect of neutralizing immunity among rAAV vectors pseudotyped with serotype 2, 5, and 8 capsids in mouse and nonhuman primate models.

March 19, 2005Molecular TherapyOpen Access

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

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Authors

ADAndrew M. DavidoffSt. Jude Children's Research Hospital JGJohn T. GrayVertex Pharmaceuticals (United States)CNCatherine Y. NgCornell University

Discussion

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Implication

Preclinical comparative study demonstrates superior liver transduction with rAAV-8 over rAAV-2 and rAAV-5 in animal models, indicating key serotype advantages for gene therapy.

Key Points

To compare the hepatic transduction efficiency, kinetics, and effect of neutralizing immunity among rAAV vectors pseudotyped with serotype 2, 5, and 8 capsids in mouse and nonhuman primate models.
Administered recombinant AAV vectors pseudotyped with capsids from serotypes 2, 5, and 8 into murine models and nonhuman primates.
Evaluated transgene expression kinetics, dose responsiveness, conversion of vector genomes to stable duplex DNA, and the inhibitory effect of preexisting serotype-specific antibodies.
In murine models, rAAV-2/8 achieved 17- to 84-fold higher transgene expression across all time points and doses compared to rAAV-2 or rAAV-5, driven by rapid conversion of single-stranded genomes to transcriptionally active duplex DNA.
In nonhuman primates, liver-directed delivery of rAAV-5 and rAAV-2/8 vectors established therapeutic levels of transgene expression.
Preexisting serotype-specific neutralizing antibodies completely prevented successful transduction, an impediment that was circumvented by switching to alternative capsid serotypes.

Cite This Study

Davidoff et al. (2005) studied this question.

synapsesocial.com/papers/6a70187975498292b70977a7 https://doi.org/10.1016/j.ymthe.2004.12.022

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March 19, 2005Molecular TherapyOpen Access

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

View Full Paper

Ask AI

Bookmark

Authors

ADAndrew M. DavidoffSt. Jude Children's Research Hospital JGJohn T. GrayVertex Pharmaceuticals (United States)CNCatherine Y. NgCornell University

Discussion

Member takes

Implication

Preclinical comparative study demonstrates superior liver transduction with rAAV-8 over rAAV-2 and rAAV-5 in animal models, indicating key serotype advantages for gene therapy.

Key Points

To compare the hepatic transduction efficiency, kinetics, and effect of neutralizing immunity among rAAV vectors pseudotyped with serotype 2, 5, and 8 capsids in mouse and nonhuman primate models.
Administered recombinant AAV vectors pseudotyped with capsids from serotypes 2, 5, and 8 into murine models and nonhuman primates.
Evaluated transgene expression kinetics, dose responsiveness, conversion of vector genomes to stable duplex DNA, and the inhibitory effect of preexisting serotype-specific antibodies.
In murine models, rAAV-2/8 achieved 17- to 84-fold higher transgene expression across all time points and doses compared to rAAV-2 or rAAV-5, driven by rapid conversion of single-stranded genomes to transcriptionally active duplex DNA.
In nonhuman primates, liver-directed delivery of rAAV-5 and rAAV-2/8 vectors established therapeutic levels of transgene expression.
Preexisting serotype-specific neutralizing antibodies completely prevented successful transduction, an impediment that was circumvented by switching to alternative capsid serotypes.

Cite This Study

Davidoff et al. (2005) studied this question.

synapsesocial.com/papers/6a70187975498292b70977a7 https://doi.org/10.1016/j.ymthe.2004.12.022

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