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An Efficient Method for Adenovirus Production
Published on: June 10, 2021
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.
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.
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.
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