Anticancer activity of an adenoviral vector expressing short hairpin RNA against BK virus T-ag

Area of Science:

• Oncology
• Virology
• Molecular Biology

Background:

• The human polyomavirus BK (BKV) is oncogenic in rodents, serving as a model for studying targeted antineoplastic therapies.
• The BKV T-antigen (T-ag) oncogene drives malignant transformation, making its suppression a potential therapeutic target.

Purpose of the Study:

• To investigate the efficacy of stable T-antigen oncogene suppression using small interfering RNAs (siRNAs) delivered via an adenovirus vector.
• To evaluate the impact of inhibiting BKV T-ag expression on the malignant phenotype of BKV-transformed mouse cells in vitro and in vivo.

Main Methods:

• Development of an adenovirus vector system for expressing small hairpin RNAs (shRNAs) targeting BKV T-ag, which are processed into siRNAs.
• In vitro and in vivo assessment of the adenovirus-mediated siRNA delivery and its effect on BKV T-ag expression.
• Evaluation of cellular changes, including growth rate, p53 activity, and apoptosis induction, following T-ag suppression.
• In vivo studies to assess the impact on tumor formation and growth of BKV-transformed cells.

Main Results:

• The adenovirus vector efficiently delivered siRNA to inhibit BKV T-ag expression both in vitro and in vivo.
• Suppression of T-ag led to reduced in vitro growth rates of transformed cells, partly due to restored p53 activity and induced apoptosis.
• Adenovirus vectors expressing anti-T-ag siRNA suppressed the tumorigenicity of BKV-transformed cells in vivo.
• Direct treatment of established tumors with the adenovirus vector significantly reduced tumor growth.

Conclusions:

• Stable suppression of BKV T-ag oncogene expression via siRNA delivered by adenovirus vectors is a viable strategy.
• This approach demonstrates potential as an in vivo anticancer tool against viral oncogenes.
• The study highlights the therapeutic potential of siRNA delivery systems for targeting oncogenic viral proteins.