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- Title
Pseudo-hydrodynamic delivery of helper-dependent adenoviral vectors into non-human primates for liver-directed gene therapy.
- Authors
Brunetti-Pierri, Nicola; Stapleton, Gary E; Palmer, Donna J; Zuo, Yu; Mane, Viraj P; Finegold, Milton J; Beaudet, Arthur L; Leland, Michelle M; Mullins, Charles E; Ng, Philip
- Abstract
Helper-dependent adenoviral vectors (HDAds) are attractive for liver-directed gene therapy because they can mediate long-term, high-level transgene expression without chronic toxicity. However, systemic delivery requires high vector doses for efficient hepatic transduction, resulting in dose-dependent acute toxicity. Clearly, strategies to improve hepatic transduction with low vector doses are needed. In this regard, we have previously shown that hydrodynamic injection of helper-dependent adenoviral vectors into mice results in increased hepatic transduction, reduced systemic vector dissemination, and reduced pro-inflammatory cytokines compared with conventional injection and thus has the potential to improve dramatically the therapeutic index of helper-dependent adenoviral vectors. Unfortunately, the rapid, large-volume injection used in this method cannot be applied to larger animals. Therefore, we have developed a novel balloon occlusion catheter-based method to mimic hydrodynamic injection of helper-dependent adenoviral vectors into non-human primates that does not require rapid, large-volume injection. Using a low, clinically relevant vector dose, this minimally invasive method results in high-efficiency hepatic transduction with minimal toxicity and stable long-term transgene expression for at least 413 days.
- Publication
Molecular therapy : the journal of the American Society of Gene Therapy, 2007, Vol 15, Issue 4, p732
- ISSN
1525-0016
- Publication type
Journal Article
- DOI
10.1038/sj.mt.6300102