Protocol

Oncolytic Viruses

Volume 797 of the series Methods in Molecular Biology pp 35-52

Date:

Construction of Targeted and Armed Oncolytic Adenoviruses

  • Konstantin DoroninAffiliated withDivision of Medical Genetics, University of Washington Email author 
  • , Dmitry M. ShayakhmetovAffiliated withUniversity of Washington

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Abstract

Oncolytic (replication-competent) adenoviruses (Ads) represent the most advanced platform for cancer gene therapy. These viral vectors ablate tumors by killing tumor cells in the process of virus replication. As progeny virions are released, they infect remaining cancer cells, generating a bystander effect. Ads engineered for increased cancer specificity produce less damage to normal tissues. First-generation oncolytic Ads have demonstrated acceptable levels of safety while the efficacy was observed only in combination with chemotherapy and/or radiation. Second-generation oncolytic Ads are armed with therapeutic transgenes to increase release, spread, and bystander effect for enhancing the efficacy. Third-generation oncolytic Ads are armed vectors with capsid modifications for transductional detargeting from normal tissues and targeting to cancer cells. Chemical modification of the capsid additionally improves therapeutic window. Here, we describe methods for generation and characterization of advanced-generation oncolytic Ads.

Key words

Adenovirus Oncolytic virotherapy Genetic vectors Animal models Experimental neoplasms