New highly potent and specific E6 and E7 siRNAs for treatment of HPV16 positive cervical cancer

K. Yamato, T. Yamada, M. Kizaki, K. Ui-Tei, Y. Natori, M. Fujino, T. Nishihara, Y. Ikeda, Y. Nasu, K. Saigo, M. Yoshinouchi

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Persistent infection by high-risk types of human papillomaviruses (HPV) is a necessary cause of cervical cancer, with HPV16 the most prevalent, accounting for more than 50% of reported cases. The virus encodes the E6 and E7 oncoproteins, whose expression is essential for maintenance of the malignant phenotype. To select efficacious siRNAs applicable to RNAi therapy for patients with HPV16+ cervical cancer, E6 and E7 siRNAs were designed using siDirect computer software, after which 10 compatible with all HPV16 variants were selected, and then extensively examined for RNAi activity and specificity using HPV16+ and HPV16-cells. Three siRNAs with the highest RNAi activities toward E6 and E7 expression, as well as specific and potent growth suppression of HPV16+ cancer cells as low as 1 nM were chosen. Growth suppression was accompanied by accumulation of p53 and p21WAF1/CIP1, as well as morphological and cytochemical changes characteristic of cellular senescence. Antitumor activity of one of the selected siRNAs was confirmed by retarded tumor growth of HPV16+ cells in NOD/SCID mice when locally injected in a complex with atelocollagen. Our results demonstrate that these E6 and E7 siRNAs are promising therapeutic agents for treatment of virus-related cancer.

Original languageEnglish
Pages (from-to)140-153
Number of pages14
JournalCancer Gene Therapy
Volume15
Issue number3
DOIs
Publication statusPublished - 2008 Mar

Fingerprint

Uterine Cervical Neoplasms
RNA Interference
Growth
Viruses
Inbred NOD Mouse
SCID Mice
Second Primary Neoplasms
Cell Aging
Oncogene Proteins
Neoplasms
Therapeutics
Software
Maintenance
Phenotype
Infection
atelocollagen
RNAi Therapeutics

Keywords

  • Cervical cancer
  • HPV16
  • siRNA therapy

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Yamato, K., Yamada, T., Kizaki, M., Ui-Tei, K., Natori, Y., Fujino, M., ... Yoshinouchi, M. (2008). New highly potent and specific E6 and E7 siRNAs for treatment of HPV16 positive cervical cancer. Cancer Gene Therapy, 15(3), 140-153. https://doi.org/10.1038/sj.cgt.7701118

New highly potent and specific E6 and E7 siRNAs for treatment of HPV16 positive cervical cancer. / Yamato, K.; Yamada, T.; Kizaki, M.; Ui-Tei, K.; Natori, Y.; Fujino, M.; Nishihara, T.; Ikeda, Y.; Nasu, Y.; Saigo, K.; Yoshinouchi, M.

In: Cancer Gene Therapy, Vol. 15, No. 3, 03.2008, p. 140-153.

Research output: Contribution to journalArticle

Yamato, K, Yamada, T, Kizaki, M, Ui-Tei, K, Natori, Y, Fujino, M, Nishihara, T, Ikeda, Y, Nasu, Y, Saigo, K & Yoshinouchi, M 2008, 'New highly potent and specific E6 and E7 siRNAs for treatment of HPV16 positive cervical cancer', Cancer Gene Therapy, vol. 15, no. 3, pp. 140-153. https://doi.org/10.1038/sj.cgt.7701118
Yamato, K. ; Yamada, T. ; Kizaki, M. ; Ui-Tei, K. ; Natori, Y. ; Fujino, M. ; Nishihara, T. ; Ikeda, Y. ; Nasu, Y. ; Saigo, K. ; Yoshinouchi, M. / New highly potent and specific E6 and E7 siRNAs for treatment of HPV16 positive cervical cancer. In: Cancer Gene Therapy. 2008 ; Vol. 15, No. 3. pp. 140-153.
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