Strategies of transcriptional regulation in retrovirus production and expression

• Processo: 01/10553-0
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Data de Início da vigência: 01 de novembro de 2001
• Data de Término da vigência: 31 de outubro de 2003
• Área de conhecimento: Ciências Biológicas - Bioquímica - Biologia Molecular
• Pesquisador responsável: Bryan Eric Strauss
• Beneficiário: Bryan Eric Strauss
• Instituição Sede: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brasil
• Vinculado ao auxílio: 00/12156-5 - Estratégias de regulação transcricional em produção e expressão de retrovírus, AP.JP
• Assunto(s): Terapia genética Retroviridae Expressão gênica Genes p53
• Palavra(s)-Chave do Pesquisador: Gene Expression | Gene Therapy | Gene Transfer | P19Arf | P53 | Retrovirus

Resumo

Gene therapy is a promising, yet elusive, method of cancer treatment. Many candidate genes, like p53, are currently being tested in clinical trials using a variety of gene delivery vehicles, such as retroviral vectors. p53 is a well characterized tumor suppressor gene that targets cell cycle arrest and apoptosis via transcriptional control of key mediators, such as p21, bcl-2 and bax. The suitability of p53 for use in gene therapy applications is well documented. Retroviral vectors have been developed as gene transfer agents since they are safe, do not elicit an immune response and are easily modified. Despite the prevalence of retroviral vectors in clinical trials, in vivo viral expression can be diminished by a variety of means. The aim of this project is to develop a pCL-based retroviral vector that has enhanced in vivo expression mediated by p53 transcriptional activation. A p53-responsive element has been inserted into the promoter region of the pCL retrovirus with the hope that viral .expression will be elevated in the presence of p53. In addition, the p53 cDNA has been placed in the virus with the expectation that the p53 protein will serve two functions: 1. Activate viral expression in vivo, and 2. Act as a powerful tumor- suppressing agent. (AU)