Construction of a multi-functional helper-dependent adenovirus based system for cancer gene therapy

Ne Long, Stephan Hardiville, Annick Pierce, Katsume Fukamachi, Mitsuru Futakuchi, David B. Alexander, Tomoyuki Shirai, Hiroyuki Tsuda

Research output: Contribution to journalArticlepeer-review

Abstract

Adenovirus holds great promise as a gene delivery system; it can hold large amounts of exogenous DNA and can be chemically and genetically modified to improve targeting to specific cells and tissues. A recombinant adenovirus construct expressing p53 is currently in clinical use as a cancer therapy in China. However, the use of adenovirus constructs in therapy is limited due to patients' strong immune response against these viruses and their gene products. To overcome this problem helper-dependent adenoviruses which do not express any viral gene products have been developed. Because the helper-dependent viruses do not express any viral gene products, a helper virus is required for their replication and encapsidation into infectious particles. This manuscript describes the construction of a prototype helper-dependent adenovirus system built such that it can be easily modified. The helper-dependent virus described here is built of a series of four cassettes, each with its own function. Furthermore, each individual cassette can be removed and replaced with a cassette with a different function. In this way, different helper-dependent viruses can be readily created. This type of system could be very useful in cancer therapy: For example, libraries of different cassettes could be maintained, allowing rapid assembly of constructs able to provide therapy for individual tumor types.

Original languageEnglish (US)
Pages (from-to)939-960
Number of pages22
JournalAsian Pacific Journal of Cancer Prevention
Volume10
Issue number5
StatePublished - 2009

Keywords

  • ADMM
  • Adenovirus
  • Cancer gene therapy
  • EVE
  • Helper-dependent

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Public Health, Environmental and Occupational Health
  • Cancer Research

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