| Autor: |
L. DE MAGISTRIS, M. OLIVIERO, G. D’AGOSTINO, F. BERGANTINO, DE SIMONE, VINCENZO |
| Přispěvatelé: |
L., DE MAGISTRIS, M., Oliviero, G., D’Agostino, F., Bergantino, DE SIMONE, Vincenzo |
| Jazyk: |
angličtina |
| Rok vydání: |
2009 |
| Předmět: |
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| Popis: |
We have constructed SV40 derived episomic vectors for gene therapy able to undergo limited replication in human cells. In our vectors, DNA replication relies on a mutated version of the LT viral protein in which the ability to interact with p53 and pRB (and consequently its transforming activity) has been selectively eliminated. Even with a non-transforming LT, eccessive replication of SV40-derived vectors in human cells may result in target cells toxicity. In order to overcome this problem we have constructed: • “Low replication rate” vectors carrying deletions of the SV40 ORI/ses regions. • “Low copy number” vectors carrying anti-LT shRNA expression cassettes. We have achieved the tissue-specificity of our vectors in two ways, by constructing: • “Wide-range replication” vectors in which the selective expression of the transgene is driven by tissue-specific promoters. • “Restricted-range replication” vectors in which the viral LT gene is under the control of tissue-specific synthetic promoters, while the transgene expression is driven by the SV40 early promoter. In both cases, the tissue-specificity of our vectors depends on short synthetic modular promoters, obtained by polymerization of naturally occourring cis-acting elements. In the most successful constructs we have combined the binding domains for tissue-specific and cell-cycle-specific transcription factors, thus obtaining promoters that are selectively active in replicating cells (regenerating tissues, stem cells and tumor cells). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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