Modification of HSV-1 to an Oncolytic Virus

Abstract

Cancer-permissive viruses or oncolytic viruses consist of either genetically engineered or naturally occurring strains that possess relatively selective replicative and/or infection abilities for cancer vs. normal cells (Chiocca, Nat Rev Cancer 2: 938–950, 2002). They can also be armed with additional anticancer cDNAs (e.g., cytokines, prodrug-activating, anti-angiogenesis genes, and others) to extend therapeutic effects (Kaur et al., Curr Gene Ther 9: 341–355, 2009). Herpes simplex virus type 1 (HSV-1) possesses several advantages as an oncolytic virus such as a rapid lytic cycle and a large capacity for insertion of heterologous DNA sequences (Wade-Martins et al., Nat Biotechnol, 19: 1067–1070, 2001). However, the technical nuances of genetic manipulation of the HSV-1 genome may still be relatively challenging. Here, we describe a system that has been durable and consistent in providing the ability to generate multiple recombinant HSV-1. The HsvQuik technology utilizes an HSV-1 genome cloned in a bacterial artificial chromosome to recombine heterologous cDNAs in a relatively rapid and reliable manner (Terada et al., Gene Ther 13: 705–714, 2006).