Herpes simplex virus 1 (HSV-1)-based vectors

Abstract

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus displaying several outstanding adaptations to the nervous system, and each of them can be rationally exploited in the design of gene therapy vectors with regard to neurological applications. Replication-competent attenuated vectors are becoming a suitable and powerful tool to eradicate brain tumors, such as malignant gliomas, due to their ability to replicate and spread only within the tumor mass, and have reached Phase II clinical trials in some cases. Replication- incompetent recombinant vectors are nontoxic gene transfer tools that preserve most of the neurotropic features of HSV- 1, particularly the ability to express genes after having established latent infections, and are thus proficient candidates for therapeutic gene transfer settings in neurons. A first clinical trial, conceived to treat cancerrelated pain, is currently being developed. Helper-dependent amplicon vectors take advantage of the capacity of the virus particle to accommodate up to 150 kbp of foreign DNA, enabling these vectors to deliver complete genomic loci to the nucleus of mammalian cells and making amplicons particularly useful in protocols where stable and physiological transgene expression is required. However, difficulties in obtaining large stocks of helper-free amplicons are hampering the use of these vectors in the clinic. This chapter summarizes current applications of HSV-1-based vectors with particular emphasis in amplicon vectors.