Biology Reference
In-Depth Information
Chapter 4
Herpes Simplex Virus 1 (HSV-1)-Based Vectors
Aldo Pourchet , Matias E. Melendez , Anna Greco , and Alberto L. Epstein
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 profi cient
candidates for therapeutic gene transfer settings in neurons. A fi rst clinical trial, conceived to treat cancer-
related 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 proto-
cols where stable and physiological transgene expression is required. However, diffi culties 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.
Key words HSV-1, Defective recombinant vectors, Attenuated recombinant vectors, Amplicon vectors
1
Basic Concepts
The improvement of methods for effi cient delivery and regulated
expression of genetic material into mammalian cells or organisms
has been a major objective of molecular and cellular biology, gene
therapy, and vaccine development over the last 30 years and is still
an area of intensive research. Viral-derived vectors are one of the
most promising gene transfer tools due to the fact that viruses are
naturally occurring molecular devices that have evolved to ensure
targeted gene delivery and effi cient expression to most cell types.
The present chapter focuses on vectors derived from herpes simplex
virus type 1 (HSV-1) and their applications in neurobiology and
gene therapy of neurological diseases. HSV-1-based vectors constitute
one of the most powerful, interesting and versatile virus-derived
gene transfer tools.
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