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

Area of Science:

• Molecular Biology
• Gene Therapy
• Biotechnology

Background:

• The tumor suppressor protein p53 plays a critical role in cellular responses to stress.
• Controlling transgene expression in viral vectors based on cellular conditions like p53 activation is a key goal in gene therapy.

Purpose of the Study:

• To develop and characterize a novel adeno-associated viral (AAV) vector, termed AAVPG, for p53-inducible transgene expression.
• To evaluate the efficacy of AAVPG as a biosensor for p53 activity under various stress conditions.

Main Methods:

• Construction of an AAV vector (AAVPG) utilizing a p53-responsive promoter (PG) to control luciferase transgene expression.
• In vitro validation of AAVPG-luc vector induction in the presence of functional p53.
• Assessment of AAVPG-luc vector response to hypoxia and biomechanical stress in vitro.
• In vivo evaluation of AAVPG-luc vector activity in tumor-bearing mice treated with doxorubicin.

Main Results:

• AAVPG-luc demonstrated significant induction of transgene expression (1038±202 fold) specifically with functional p53.
• The vector served as an effective biosensor for p53 activation under hypoxia (4.48±0.6 fold) and biomechanical stress (2.53±0.4 fold).
• In vivo studies showed a significant increase in AAVPG-luc activity post-doxorubicin treatment in tumor-bearing mice.

Conclusions:

• The AAVPG vector system enables on-demand transgene expression regulated by p53.
• AAVPG functions as a sensitive biosensor for detecting p53 activation in vitro and in vivo.
• This vector holds promise for applications requiring stress-inducible gene expression and monitoring p53 pathway activity.