Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Google Scholar, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

A novel gene transfer strategy that combines promoter and transgene activities for improved tumor cell inhibition

Texto completo
Autor(es):
Strauss‚ B.E. ; Bajgelman‚ M.C. ; Costanzi-Strauss‚ E.
Número total de Autores: 3
Tipo de documento: Artigo Científico
Fonte: Cancer Gene Therapy; v. 12, n. 12, p. 935-946, 2005.
Resumo

Typically, gene transfer strategies utilize a promoter/transgene arrangement that treat these elements independently and do not offer any interplay between them. Our goal was to establish a promoter/transgene combination that would result in improvement in both expression and therapeutic effect by utilizing the transcriptional properties of p53 to drive its own expression as well as act as a tumor suppressor. The pCL retroviral system was modified in the U3 region of the 3' LTR by the addition of a p53-responsive sequence (the PG element), creating the pCLPG system. Upon reverse transcription, the 5' LTR is converted, as shown here, to a p53-dependent promoter. We also show, using a temperature-sensitive model, that the pCLPG system could be driven by p53 encoded within the virus construct and expression was modulated depending on the p53 phenotype, demonstrating a regulatory feedback loop. Moreover, the pCLPG system was shown to express the transgene at a higher level and to inhibit tumor cell proliferation more robustly than the original pCL system. This novel system employs the transgene to serve two purposes, drive viral expression and inhibit tumor cell proliferation. The pCLPG vectors represent a new gene transfer strategy of synergizing the promoter and transgene activities. (AU)

Processo FAPESP: 98/15120-0 - Eficiente transferência de genes de controle do ciclo celular mediada por uma aperfeiçoada plataforma de Retrovírus do sistema pCL: aplicações in vitro e in vivo
Beneficiário:Eugenia Costanzi-Strauss
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 00/12156-5 - Estratégias de regulação transcricional em produção e expressão de retrovírus
Beneficiário:Bryan Eric Strauss
Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores