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- Title
A novel system for mitigation of ectopic transgene expression induced by adenoviral vectors.
- Authors
Reynolds, P N; Holmes, M D; Adachi, Y; Kaliberova, L; Curiel, D T
- Abstract
Adenoviral (Ad) vectors are good candidates for gene therapy in view of their high in vivo gene delivery efficiency. However, greater control over the tissue distribution of transgene expression is required to avoid potentially deleterious effects in non-target organs. In this regard, the liver is particularly at risk due to the high natural tropism of Ad for this organ, where dose limiting toxicity has been seen due to toxic transgene expression. We hypothesized that the cre/IoxP system could be utilized to reduce unintended transgene expression at this site. This concept was tested using an Ad vector (AdLCLLL) carrying a reporter gene cassette in which the promoter and luciferase gene were flanked by LoxP sequences. Co-administration of this vector with a second vector carrying the cre recombinase gene in vitro and in vivo resulted in specific down-regulation of transgene expression. This novel approach thus has the potential to improve the safety of gene therapy strategies that rely upon the defivery of genes which may be hepatotoxic.
- Subjects
ADENOVIRUSES; GENE therapy; LIVER
- Publication
Gene Therapy, 2001, Vol 8, Issue 16, p1271
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301511