Local Delivery of a Viral Vector Mitigates Neutralization by Antiviral Antibodies and Results in Efficient Transduction of Rabbit Liver
Molecular Therapy, ISSN: 1525-0016, Vol: 12, Issue: 6, Page: 1043-1051
2005
- 19Citations
- 5Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations19
- Citation Indexes18
- 18
- CrossRef13
- Patent Family Citations1
- 1
- Captures5
- Readers5
Article Description
Antiviral antibodies within the human population remain a barrier to the effective clinical use of viral gene transfer vectors. We have asked whether local, balloon catheter-mediated delivery of a viral vector to the rabbit liver using a hepatic vein might mitigate the neutralizing effects of antiviral antibodies. We have compared directly the ability of adenovirus (Ad2) encoding nuclear-localized β-galactosidase to infect the rabbit liver after local and systemic delivery in both the presence and the absence of defined anti-Ad2 antibody titers. In naive rabbits, local delivery resulted in higher β-galactosidase expression compared to systemic delivery. In the presence of passively administered anti-Ad2 antibodies, local delivery resulted in expression levels that were comparable to those obtained in naive rabbits by systemic delivery. Local delivery also resulted in the majority of expression originating from hepatocytes, even in passively immunized animals, a result that could not be duplicated using the systemic approach. Since systemic delivery of adenovirus in naive animal models results in transgene expression levels often regarded as therapeutic, these results predict that local hepatic vein delivery of a viral vector is a clinically practical approach to mitigate neutralizing antiviral antibodies and generate therapeutic levels of transgene expression.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S1525001605010270; http://dx.doi.org/10.1016/j.ymthe.2005.06.475; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=28444490673&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/16139571; https://linkinghub.elsevier.com/retrieve/pii/S1525001605010270; https://dx.doi.org/10.1016/j.ymthe.2005.06.475
Elsevier BV
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