Oncolytic Viruses: The Power of Directed Evolution

Attempts at developing oncolytic viruses have been primarily based on rational design. However, this approach has been met with limited success. An alternative approach employs directed evolution as a means of producing highly selective and potent anticancer viruses. In this method, diverse viruses...

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Main Authors: Maxine Bauzon, Terry W. Hermiston
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Advances in Virology
Online Access:http://dx.doi.org/10.1155/2012/586389
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author Maxine Bauzon
Terry W. Hermiston
author_facet Maxine Bauzon
Terry W. Hermiston
author_sort Maxine Bauzon
collection DOAJ
description Attempts at developing oncolytic viruses have been primarily based on rational design. However, this approach has been met with limited success. An alternative approach employs directed evolution as a means of producing highly selective and potent anticancer viruses. In this method, diverse viruses are grown under conditions that maximize diversity and then passaged under conditions meant to mimic those encountered in the human cancer microenvironment. Viruses which evolve to thrive under this selective pressure are isolated and tested to identify those with increased potency (i.e., ability to replicate and spread) and/or an increased therapeutic window (i.e., differentiated replication and spread on tumor versus normal cells), both of which have potential value but the latter of which defines an oncolytic virus. Using ColoAd1, an oncolytic virus derived by this approach as a prototype, we highlight the benefits of directed evolution, discuss methods to “arm” these novel viruses, and introduce techniques for their genetic modulation and control.
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spelling doaj-art-9e47241441fd4a938e911da665c59f402025-02-03T01:00:29ZengWileyAdvances in Virology1687-86391687-86472012-01-01201210.1155/2012/586389586389Oncolytic Viruses: The Power of Directed EvolutionMaxine Bauzon0Terry W. Hermiston1Bayer Healthcare, Biologics Research, 455 Mission Bay Boulevard South, San Francisco, CA 94158, USABayer Healthcare, Biologics Research, 455 Mission Bay Boulevard South, San Francisco, CA 94158, USAAttempts at developing oncolytic viruses have been primarily based on rational design. However, this approach has been met with limited success. An alternative approach employs directed evolution as a means of producing highly selective and potent anticancer viruses. In this method, diverse viruses are grown under conditions that maximize diversity and then passaged under conditions meant to mimic those encountered in the human cancer microenvironment. Viruses which evolve to thrive under this selective pressure are isolated and tested to identify those with increased potency (i.e., ability to replicate and spread) and/or an increased therapeutic window (i.e., differentiated replication and spread on tumor versus normal cells), both of which have potential value but the latter of which defines an oncolytic virus. Using ColoAd1, an oncolytic virus derived by this approach as a prototype, we highlight the benefits of directed evolution, discuss methods to “arm” these novel viruses, and introduce techniques for their genetic modulation and control.http://dx.doi.org/10.1155/2012/586389
spellingShingle Maxine Bauzon
Terry W. Hermiston
Oncolytic Viruses: The Power of Directed Evolution
Advances in Virology
title Oncolytic Viruses: The Power of Directed Evolution
title_full Oncolytic Viruses: The Power of Directed Evolution
title_fullStr Oncolytic Viruses: The Power of Directed Evolution
title_full_unstemmed Oncolytic Viruses: The Power of Directed Evolution
title_short Oncolytic Viruses: The Power of Directed Evolution
title_sort oncolytic viruses the power of directed evolution
url http://dx.doi.org/10.1155/2012/586389
work_keys_str_mv AT maxinebauzon oncolyticvirusesthepowerofdirectedevolution
AT terrywhermiston oncolyticvirusesthepowerofdirectedevolution