Lytic virus infection results in production of a virus progeny and lysis of the infected cell. Tumor cells are usually more sensitive to virus infection. Studies indicate that viral oncolysis provides a promising alternative approach to cancer therapy. The ability of viruses to selectively kill cancer cells is long known, but construction of virus variants with an improved therapeutic potential was impossible until recent advances in virus and cell molecular biology and the development of modern methods for directed modification of viruses. Adenoviruses are one of the best studied models of oncolytic viruses. These DNA viruses are convenient for genetic manipulation and show minimal pathogenicity. The review summarizes the data on the directions and approaches to generation of highly efficient variants of oncolytic adenoviruses. The approaches include introduction of directed genetic modifications into the virus genome, accelerated selection of oncolytic virus variants following treatment with mutagens, the use of adenoviruses as vectors to introduce therapeutic gene products, optimization of viral delivery systems, minimization of the negative effects from the host immune system, etc. The dynamic development of studies in the field holds promise that many variants of oncolytic adenoviruses will find clinical application in the nearest future.
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ACKNOWLEDGMENTS This work was supported by the Ministry of Educa tion and Science (Agreement no. 11.G34.31.0034 “New Approaches to Drug Design: Search for, Selec tion, and Construction of Virus Strains Nonpatho genic to Humans and Promising as Oncolytic Drugs” with Novosibirsk State University), the Russian Foun dation for Basic Research (project nos. 11 04 0410 and 11 04 92697), and the program “Molecular and Cell Biology” of the Presidium of the Russian Acad emy of Sciences.
- gene therapy
- oncolytic adenoviruses