Herpes simplex virus type 1-based amplicon vector systems

Abstract

Publisher Summary This chapter discusses the development of the herpes simplex virus type 1 (HSV-1) amplicon as an efficient gene transfer vehicle, with emphasis on recent advances that have reduced toxic effects associated with the vector and increased both the efficiency of gene transfer and the stability of gene expression. HSV-1-based amplicon vectors have a great potential for applications in gene therapy, because they have a large transgene capacity and can efficiently transduce most cell types, both dividing and nondividing. The HSV-1 amplicon contains three types of genetic elements—namely, (1) sequences that allow its propagation as a bacterial plasmid, (2) a transgene cassette with the genes of interest, and (3) ∼1% of the 152-kb HSV-1 genome, in particular an origin of DNA replication and a DNA cleavage/packaging signal. These two noncoding, cis-acting HSV-1 elements are sufficient for supporting the replication of amplicon DNA and subsequent packaging into HSV-1 virions in the presence of helper functions. HSV-1, a member of the subfamily Alphaherpesvirinae , is a common pathogen in humans and one of the most extensively characterized viruses. The lytic cycle of the HSV-1 infection usually causes only mild symptoms, such as cold sores, and is rapidly controlled by the immune system.