Adenovirus Biology, Recombinant Adenovirus, and Adenovirus Usage in Gene Therapy

Maki Watanabe1, Yuya Nishikawaji1, Hirotaka Kawakami1

  • 1Department of Gene Therapy and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.

Viruses
|December 28, 2021
PubMed

Insights

Gene therapy using oncolytic viruses (OV) shows promise for cancer treatment. Researchers developed a new technology for creating multi-factor conditionally replicating adenoviruses (m-CRAs) to improve safety and efficacy in cancer therapy.

Area of Science:

  • Virology
  • Oncology
  • Regenerative Medicine

Background:

  • Gene therapy, including oncolytic viruses (OV) and COVID-19 vaccines, is gaining prominence.
  • Recombinant adenoviruses are key tools in cancer gene therapy and vaccine development.
  • Pluripotent stem cell (PSC)-based regenerative medicine faces ongoing technological challenges.

Purpose of the Study:

  • To review adenovirus biology, recombinant adenovirus construction, and therapeutic applications.
  • To introduce a novel technology for constructing multi-factor conditionally replicating adenoviruses (m-CRAs).
  • To explore recombinant adenovirus applications in PSC-based regenerative medicine.

Main Methods:

  • Review of wild-type adenovirus biology and recombinant adenovirus construction principles.
  • Description of a technology platform for engineering m-CRAs by modifying the adenoviral E1 region.
  • Screening of m-CRAs to identify effective candidates, such as survivin-responsive m-CRA (Surv.m-CRA).

Main Results:

  • The m-CRA technology enables modification of the adenoviral E1 region for enhanced tumor-specific replication.
  • Survivin-responsive m-CRA (Surv.m-CRA) was identified as a highly effective m-CRA.
  • Clinical trials for Surv.m-CRA in cancer patients are currently in progress.

Conclusions:

  • The developed m-CRA technology offers a platform for creating safer and more effective oncolytic adenoviruses.
  • Recombinant adenoviruses hold significant potential for advancing cancer therapy and regenerative medicine.
  • Further research and clinical trials are essential to fully realize the therapeutic benefits of these technologies.