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- W2282334166 abstract "Gene therapy present a great therapeutic potential for a diversity of liver disorders including inherited metabolic conditions (phenylketonuria, tyrosinemia) and acquired diseases (chronic infections, primary and metastatic tumors). For many of these applications, vectors allowing prolonged, regulable and tissue-specific expression of the transgene would be required.Adenovirus is the most widely used vector in human clinical assay. To avoid the cellular immune response induced by first and second generation Ad, the third-generation vectors was generated, also called gutless or helper-dependent. To produce these vectors requires three basic elements: a gutless adenovirus with a therapeutic or marker gene of interest, a helper adenovirus which provide viral proteins in trans and, a cell line permissive for Ad production. Gutless adenovirus does not contain any viral region, not cellular immune response generated and can accommodate up to 36 Kbp and was demonstrated that the expression of genes that can incorporate lifelong body.In this study, two distinct gutless adenoviruses were produced, with hepatospecific and regulated expression by the RU inducible system, containing a combination of OSM and IFN genes (HCA-RUIO) and the other the hIL-12 gene (HCA-RUhIL12). After in vitro testing the correct functionality of the vectors were carried out in vivo tests in mice and hamsters. It showed that in vivo expression of gene of interest changes with the species of animal used and the transgene present in the vector. In contrast to previous data that showed in mice infected with HCA-RUmIL12 that mIL-12 can be expressed even after more than a year, in Hamsters, the same vector expressed the transgene only after the first induction with RU and then it could not be detected. The vector HCA-RUIO gave a similar pattern of expression of the transgene in both hamsters, but also in mice. This may be due to the fact that if the protein products by the vector are exogenous to the organism is activated immunostimolatory activity in animals that leads to the elimination of the transfected cells and thus an inability to reinduce the expression of the transgene." @default.
- W2282334166 created "2016-06-24" @default.
- W2282334166 creator A5072876278 @default.
- W2282334166 date "2011-01-27" @default.
- W2282334166 modified "2023-09-24" @default.
- W2282334166 title "Construction and evaluation of high-capacity adenoviral vectors for gene therapy applications" @default.
- W2282334166 hasPublicationYear "2011" @default.
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