Recent advances in the development of oncolytic HSV-1 vectors: 'arming' of HSV-1 vectors and application of bacterial artificial chromosome technology for their construction.
HSV-1 was one of the first oncolytic viruses to have been investigated for its therapeutic potential against cancer. Among the dozens of oncolytic HSV-1 vectors that have so far been reported, some carry transgenes, including interleukins, anti-angiogenic peptides, and prodrug-converting enzymes. 'Arming' of HSV-1 with therapeutic transgenes such as these is expected to enhance its efficacy. HSV-1 is a 152-kb double-stranded DNA virus, and the generation of armed HSV usually takes several months to achieve by conventional homologous recombination methods. Recently, bacterial artificial chromosome (BAC)-based systems termed 'HSVQuik' and 'Flip-Flop HSV-BAC' were developed to enable the fast generation of recombinant HSV-1 vectors within weeks by using site-specific recombinases. These systems provide powerful tools for screening potential transgenes that might greatly enhance the efficacy of HSV-1 vectors. This review discusses the current state of research into the development of oncolytic HSV-1 vectors, and highlights the promise that armed oncolytic HSV-1 vectors might hold for the future.
Jeyaretna
Deva S
DS
Massachusetts General Hospital, Molecular Neurosurgery Laboratory, Department of Neurosurgery, Boston, MA 02114, USA.
Kuroda
Toshihiko
T
D000818:Animals; D022202:Chromosomes, Artificial, Bacterial; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000138:chemical synthesis*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D050504:Oncolytic Viruses / Q000235:genetics*