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

Author(s)

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

Affiliation

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

• Document type: Journal article
• Source: VIROLOGY; v. 447, n. 1-2, p. 166-171, DEC 2013.
• Web of Science Citations: 5

Abstract

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)

• FAPESP's process: 10/03958-2 - Employment of IFN-beta and the p53/Arf pathway for the development of a new immunotherapy for melanoma
• Grantee: Ruan Felipe Vieira Medrano
• Support Opportunities: Scholarships in Brazil - Master