AAVPG: A vigilant vector where transgene expression is induced by p53

Autor(es)

Bajgelman, Marcio C. ^[1] ; Medrano, Ruan F. V. ^[1] ; Carvalho, Anna Carolina P. V. ^[1] ; Strauss, Bryan E. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Lab Genet & Mol Cardiol LIM13, Viral Vector Lab, Heart Inst, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: VIROLOGY; v. 447, n. 1-2, p. 166-171, DEC 2013.
• Citações Web of Science: 5

Resumo

Using p53 to drive transgene expression from viral vectors may provide on demand expression in response to physiologic stress, such as hypoxia or DNA damage. Here we introduce AAVPG, an adeno-associated viral (AAV) vector where a p53-responsive promoter, termed PG, is used to control transgene expression. In vitro assays show that expression from the AAVPG-luc vector was induced specifically in the presence of functional p53 (1038 +/- 202 fold increase, p < 0.001). The AAVPG-Iuc vector was an effective biosensor of p53 activation in response to hypoxia (4.48 +/- 0.6 fold increase in the presence of 250 mu M CoCl2, p < 0.001) and biomechanical stress (253 +/- 0.4 fold increase with stretching, p < 0.05). In vivo, the vigilant nature of the AAVPG-luc vector was revealed after treatment of tumor-bearing mice with doxorubicin (pretreatment, 3.4 x 10(5) +/- 0.43 x 10(5) photons/s; post-treatment, 6.6 x 10(5) +/- 2.1 x 10(5) photons/s, p < 0.05). These results indicate that the AAVPG vector is an interesting option for detecting p53 activity both in vitro and in vivo. (C) 2013 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 11/50911-4 - Elucidacao dos mecanismos moleculares que mediam a resposta da celulas de melanoma para a atividade combinada das vias de p53/arf e ifnb.
• Beneficiário: Bryan Eric Strauss
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/50210-0 - Combinacoes estrategicas entre os promotores virais e transgenes destinadas a terapia genica do cancer.
• Beneficiário: Bryan Eric Strauss
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/54480-2 - Desenvolvimento de uma nova estratégia baseada em terapia gênica por demanda para prevenir a deterioração da função cardíaca associada à hipertrofia
• Beneficiário: Marcio Chaim Bajgelman
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 10/03958-2 - Utilização do IFN-beta e da via p53/Arf na elaboração de uma nova imunoterapia para melanoma
• Beneficiário: Ruan Felipe Vieira Medrano
• Modalidade de apoio: Bolsas no Brasil - Mestrado