Development of an adenoviral vector with robust expression driven by p53

Journal Article · Tue Feb 05 04:00:00 EST 2008 · Virology

DOI:https://doi.org/10.1016/j.virol.2007.11.015· OSTI ID:21078015

Bajgelman, Marcio C ^[1]; Strauss, Bryan E ^[1]

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1. Viral Vector Group, Laboratory of Genetics and Molecular Cardiology/LIM 13, Heart Institute (InCor), University of Sao Paulo School of Medicine (Brazil)

Here we introduce a new adenoviral vector where transgene expression is driven by p53. We first developed a synthetic promoter, referred to as PGTx{beta}, containing a p53-responsive element, a minimal promoter and the first intron of the rabbit {beta}-globin gene. Initial assays using plasmid-based vectors indicated that expression was tightly controlled by p53 and was 5-fold stronger than the constitutive CMV immediate early promoter/enhancer. The adenoviral vector, AdPG, was also shown to offer p53-responsive expression in prostate carcinoma cells LNCaP (wt p53), DU-145 (temperature sensitive mutant of p53) and PC3 (p53-null, but engineered to express temperature-sensitive p53 mutants). AdPG served as a sensor of p53 activity in LNCaP cells treated with chemotherapeutic agents. Since p53 can be induced by radiotherapy and chemotherapy, this new vector could be further developed for use in combination with conventional therapies to bring about cooperation between the genetic and pharmacologic treatment modalities.

• OSTI ID: 21078015
• Journal Information: Virology, Journal Name: Virology Journal Issue: 1 Vol. 371; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADENOVIRUS
CARCINOMAS
CHEMOTHERAPY
DOXORUBICIN
GENE THERAPY
GLOBINS
MUTANTS
PROMOTERS
PROSTATE
RABBITS
RADIOTHERAPY
VECTORS