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Antisense RNA directed to the human papillomavirus type 16 E7 mRNA from herpes simplex virus type 1 derived vectors

Ilkka Kari1, Stina Syrjänen, Bo Johansson

  • 1Department of Virology, Institute of Dentistry, University of Turku, Turku, Finland. ilanka@utu.fi

Virology Journal
|June 6, 2007
PubMed
Abstract

Insights

Herpes simplex virus (HSV) vectors expressing antisense RNA effectively reduced human papillomavirus (HPV) oncogene E7 mRNA and protein in cervical cancer cells. This suggests HSV vectors show promise for HPV gene therapy.

Area of Science:

  • Oncology
  • Virology
  • Gene Therapy

Background:

  • Human papillomavirus (HPV) is a primary cause of cervical cancer.
  • Current treatments lack HPV-specific therapies for invasive cervical cancer and precursor lesions.

Purpose of the Study:

  • To investigate the potential of herpes simplex virus (HSV) vectors for expressing antisense RNA targeting the HPV-16 E7 oncogene.

Main Methods:

  • Constructed replication-competent, nonneuroinvasive HSV-1 vectors lacking the gamma134.5 gene.
  • Vectors expressed RNA antisense to the HPV-16 E7 gene's initial 100 nucleotides.
  • Assayed E7 mRNA and protein downregulation in HPV-16 positive CaSki cells using R5225 (tk-) and R5226 (tk+) vectors.

Main Results:

  • Both HSV vectors successfully produced antisense E7 RNA in a dose-dependent manner.
  • Expression of HPV-16 E7 mRNA was significantly downregulated in CaSki cells infected with R5225 or R5226.
  • The tk+ recombinant vector (R5226) effectively downregulated E7 protein expression.

Conclusions:

  • Antisense RNA delivered via HSV vectors efficiently reduced HPV-16 E7 mRNA and protein levels in CaSki cells.
  • HSV vectors represent a potential therapeutic tool for gene therapy targeting HPV infections.

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