Development of a Novel Oncolytic Adenovirus Expressing a Short-hairpin RNA against Cullin 4A

Keisaku Wakabayashi, Fuminori Sakurai, Ryosuke Ono, Toshiyoshi Fujiwara, Hiroyuki Mizuguchi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Arming of an oncolytic adenovirus (OAd) by inserting expression cassettes of therapeutic transgenes into the OAd genome is a promising approach to enhance the therapeutic effects of an OAd. Ideally, this approach would simultaneously promote the replication of an OAd in tumor cells and transgene product-mediated antitumor effects by expressing therapeutic transgenes. We previously demonstrated that knockdown of cullin 4A (CUL4A), which is an E3 ubiquitin ligase, significantly promoted adenovirus replication by increasing the c-JUN protein level. In addition, previous studies reported that CUL4A was highly expressed in various types of tumor, and was involved in tumor growth and metastasis. Materials and Methods: In this study, we developed a novel OAd expressing a short-hairpin RNA (shRNA) against CUL4A (OAdshCUL4A). Results: OAd-shCUL4 mediated higher levels of cytotoxic effects on various types of human tumor cell than a conventional OAd. Higher levels of OAd genome copy numbers were found in the tumor cells for OAd-shCUL4A, compared with a conventional OAd. Conclusion: OAdshCUL4A showed efficient antitumor effects by both enhancing OAd replication and inhibiting tumor cell growth.

Original languageEnglish
Pages (from-to)161-168
Number of pages8
JournalAnticancer research
Volume40
Issue number1
DOIs
Publication statusPublished - 2020
Externally publishedYes

Keywords

  • Adenovirus
  • CUL4A
  • Oncolytic virus
  • ShRNA
  • Virotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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