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| Item Type: | Article |
|---|---|
| Title: | Vigilant vectors: adeno-associated virus with a biosensor to switch on amplified therapeutic genes in specific tissues in life-threatening diseases |
| Creators Name: | Tang, Y., Schmitt-Ott, K., Qian, K., Kagiyama, S. and Phillips, M.I. |
| Abstract: | There are many life-threatening and chronic diseases in which physiological signals could be used to switch on therapeutic protective genes. We are developing a gene therapy approach in which a systemically injected "vigilant vector" waits for these signals and switches on genes to protect specific tissues with high amplification. The concept of a vigilant vector requires four components. The first component is a safe and stable vector that can be administered by systemic injection and express transgenes in a particular organ or tissue. The adeno-associated virus vector is safe and stable for this purpose. The second component is a reversible gene switch which is a biosensor that can detect certain physiological signals. We are developing a hypoxia switch, based on the oxygen-dependent degradation domain of hypoxia-inducible factor. The third component is a tissue-specific promoter, and we have used the myosin light-chain-2V promoter for specific expression in the heart. The fourth component is an amplification system. For this we have developed a double-plasmid/vector system based on the yeast GAL4 and human transcriptional activator p65 to produce a transactivating fusion protein that binds to a GAL4 activation sequence in an activating plasmid that then expresses high levels of cardioprotective genes. |
| Keywords: | Vigilant Vector, Adeno-Associated Virus, Cardioprotection, Hypoxia, Hypoxia-Inducible Factor, Myosin Light-Chain Promoter, Double Plasmid, Animals, Rats |
| Source: | Methods |
| ISSN: | 1046-2023 |
| Publisher: | Elsevier / Academic Press |
| Volume: | 28 |
| Number: | 2 |
| Page Range: | 259-266 |
| Date: | October 2002 |
| Official Publication: | https://doi.org/10.1016/S1046-2023(02)00231-1 |
| PubMed: | View item in PubMed |
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