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

S. Sabbioni, E. Callegari, R. Spizzo, A. Veronese, G. Altavilla, A. Corallini, M. Negrini

Research output: Contribution to journalArticle

Abstract

The human polyomavirus BK (BKV) is oncogenic in rodents and induces malignant transformation of rodent cells in vitro. Although its role in human tumorigenesis is still debated, BKV represents an excellent model to evaluate molecularly targeted antineoplastic approaches. Here, we have tested whether stable suppression of the T antigen (T-ag) oncogene expression could inhibit the in vitro and in vivo malignant phenotype of BKV-transformed mouse cells. An adenovirus vector system that expresses small hairpin RNAs (shRNAs), which are converted into active small interfering RNAs (siRNA) molecules against the BKV T-ag, was developed. This vector was able to inhibit the expression of BKV T-ag through a highly efficient in vitro and in vivo delivery of the siRNA molecule. In addition, it allowed a stable expression of siRNA for a period of time sufficient to elicit a biological effect. Inhibition of T-ag expression results in reduction of the in vitro growth rate of BKV-transformed cells, which is, at least in part, caused by restoration of p53 activity and induction of apoptosis. In vivo studies proved that adenovirus vectors expressing anti-T-ag siRNA were able to suppress tumorigenicity of BKV-transformed cells. Moreover, adenovirus vector direct treatment of growing tumors resulted in a significant reduction of tumor growth. This study indicates that siRNAs delivery via a viral vector have a potential usefulness as in vivo anticancer tool against viral and cellular oncogenes.

Original languageEnglish
Pages (from-to)297-305
Number of pages9
JournalCancer Gene Therapy
Volume14
Issue number3
DOIs
Publication statusPublished - Mar 2007

Keywords

  • Adenovirus vector
  • BK virus
  • Short heteroduplex RNA

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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    Sabbioni, S., Callegari, E., Spizzo, R., Veronese, A., Altavilla, G., Corallini, A., & Negrini, M. (2007). Anticancer activity of an adenoviral vector expressing short hairpin RNA against BK virus T-ag. Cancer Gene Therapy, 14(3), 297-305. https://doi.org/10.1038/sj.cgt.7701014