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Death switch for gene therapy: application to erythropoietin transgene expression
Provedor de dados: 56
Autores: Souza,D.S.; Spencer,D.M.; Salles,T.S.I.; Salomão,M.A.; Payen,E.; Beuzard,Y.; Carvalho,H.F.; Costa,F.F.; Saad,S.T.Olalla.
The effectiveness of the caspase-9-based artificial "death switch" as a safety measure for gene therapy based on the erythropoietin (Epo) hormone was tested in vitro and in vivo using the chemical inducer of dimerization, AP20187. Plasmids encoding the dimeric murine Epo, the tetracycline-controlled transactivator and inducible caspase 9 (ptet-mEpoD, ptet-tTAk and pSH1/Sn-E-Fv’-Fvls-casp9-E, respectively) were used in this study. AP20187 induced apoptosis of iCasp9-modified C2C12 myoblasts. In vivo, two groups of male C57BI/6 mice, 8-12 weeks old, were injected intramuscularly with 5 µg/50 g ptet-mEpoD and 0.5 µg/50 g ptet-tTAk. There were 20 animals in group 1 and 36 animals in group 2. Animals from group 2 were also injected with the 6 µg/50 g iCasp9...
Tipo: Info:eu-repo/semantics/article
Palavras-chave: Gene therapy; Erythropoietin; Death switch; Caspase 9; AP20187; Anemia.
Ano: 2010
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010000700005