A Modular Set of Helper-Dependent Herpes Simplex Virus Expression Vectors

Herpes simplex virus (HSV) has many favorable properties in terms of its potential to serve as a delivery and expression platform for gene-based therapies, including the ability to establish persistent infections, a broad tissue tropism, episomal maintenance of transduced genes, and a large genome that can incorporate many additional cDNAs. Helper-dependent HSV vectors (commonly known as HSV amplicons) are well positioned to exploit the biology of the virus, since they contain only the two cis elements required for HSV replication and packaging and thus do not require the silencing of any viral genes to prevent toxicity to transduced cells over the course of cDNA expression. In this report we describe the development of a set of modular HSV amplicon vectors that can easily be modified to incorporate different genetic elements or alternatively can be used to retrofit existing expression constructs such that they can be packaged into infectious HSV particles.