What question did this study set out to answer?

Determine the relative abundance of integrated versus extrachromosomal rAAV genomes in the liver and assess their individual contributions to sustained hepatic transgene expression.

August 1, 2001Journal of VirologyOpen Access

Extrachromosomal Recombinant Adeno-Associated Virus Vector Genomes Are Primarily Responsible for Stable Liver Transduction In Vivo

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Authors

HNHiroyuki NakaiOregon Health & Science University SYStephen R. YantGilead Sciences (United States)TSTheresa A. StormInstitute for Stem Cell Biology and Regenerative Medicine

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Implication

In vivo animal study demonstrates extrachromosomal rAAV genomes mediate stable liver gene expression in mice, indicating reduced insertional mutagenesis risks.

Key Points

Determine the relative abundance of integrated versus extrachromosomal rAAV genomes in the liver and assess their individual contributions to sustained hepatic transgene expression.
Administered portal vein injections of hF.IX-expressing rAAV vectors (2.4 x 10^11 to 3.0 x 10^11 vector genomes per mouse, n=12) or an integrating transposon vector into mice.
Conducted a surgical two-thirds partial hepatectomy 6 weeks to 12 months after injection to induce hepatocellular regeneration and selectively dilute non-integrated DNA.
Quantified post-hepatectomy plasma hF.IX levels and remaining vector genome copy numbers per cell to evaluate genome integration and expression stability.
Following partial hepatectomy, plasma hF.IX concentrations fell by 92% and the average number of vector genomes per cell dropped by 86% in rAAV-treated mice (n=12), whereas transposon-derived hF.IX levels remained unchanged.
Extrachromosomal genomes constituted approximately 90% of stably transduced vector genomes, with integrated forms accounting for no more than ~10% in most mice.
In a separate cohort receiving higher rAAV doses, one of three mice exhibited 67% integrated vector genomes.

Cite This Study

Nakai et al. (2001) studied this question.

synapsesocial.com/papers/6a1219668edbaba0bf66a6d2 https://doi.org/10.1128/jvi.75.15.6969-6976.2001

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Implication

In vivo animal study demonstrates extrachromosomal rAAV genomes mediate stable liver gene expression in mice, indicating reduced insertional mutagenesis risks.

Extrachromosomal Recombinant Adeno-Associated Virus Vector Genomes Are Primarily Responsible for Stable Liver Transduction In Vivo

Discussion

Member takes

Implication

Key Points

Cite This Study

Extrachromosomal Recombinant Adeno-Associated Virus Vector Genomes Are Primarily Responsible for Stable Liver Transduction In Vivo

Discussion

Member takes

Implication

Key Points

Cite This Study

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