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

Viruses. 2021 Dec 14;13(12):2502. doi: 10.3390/v13122502.

Abstract

Gene therapy is currently in the public spotlight. Several gene therapy products, including oncolytic virus (OV), which predominantly replicates in and kills cancer cells, and COVID-19 vaccines have recently been commercialized. Recombinant adenoviruses, including replication-defective adenoviral vector and conditionally replicating adenovirus (CRA; oncolytic adenovirus), have been extensively studied and used in clinical trials for cancer and vaccines. Here, we review the biology of wild-type adenoviruses, the methodological principle for constructing recombinant adenoviruses, therapeutic applications of recombinant adenoviruses, and new technologies in pluripotent stem cell (PSC)-based regenerative medicine. Moreover, this article describes the technology platform for efficient construction of diverse "CRAs that can specifically target tumors with multiple factors" (m-CRAs). This technology allows for modification of four parts in the adenoviral E1 region and the subsequent insertion of a therapeutic gene and promoter to enhance cancer-specific viral replication (i.e., safety) as well as therapeutic effects. The screening study using the m-CRA technology successfully identified survivin-responsive m-CRA (Surv.m-CRA) as among the best m-CRAs, and clinical trials of Surv.m-CRA are underway for patients with cancer. This article also describes new recombinant adenovirus-based technologies for solving issues in PSC-based regenerative medicine.

Keywords: adenovirus; cancer immunotherapy; conditionally replicating adenovirus; cytokine; gene therapy; m-CRA; oncolytic virus; pluripotent stem cells; replication-defective adenoviral vector; survivin; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / physiology*
  • Adenoviridae Infections / virology*
  • Animals
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines
  • Cell Line, Tumor
  • Gene Expression
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Immunotherapy
  • Oncolytic Viruses / genetics
  • Pluripotent Stem Cells
  • Promoter Regions, Genetic
  • SARS-CoV-2
  • Survivin
  • Virus Replication

Substances

  • COVID-19 Vaccines
  • Survivin