Dj. Fink et al., ADVANCES IN THE DEVELOPMENT OF HERPES-SIMPLEX VIRUS-BASED GENE-TRANSFER VECTORS FOR THE NERVOUS-SYSTEM, Clinical neuroscience, 3(5), 1996, pp. 284-291
Herpes simplex virus (HSV) is an attractive candidate vector for treat
ment of nervous system disease by gene therapy Here we review molecula
r aspects of the natural biology of HSV as it relates to vector design
and application. Although gene transfer and transient expression was
readily achieved using first generation replication defective HSV vect
ors, these vectors did not provide for long-term transgene expression,
a prerequisite for effective treatment of neurodegenerative disease.
The principal impediments to effective use of HSV vectors are residual
toxicity of non-replicating vectors and the silencing of transgene ex
pression from persisting latent viral genomes in neurons. Recent advan
ces suggest that vectors deleted for multiple immediate early viral ge
nes provide a solution to both of these problems and thereby provide f
or the first time insight into methods for the effective design of use
ful gene vectors for central nervous system applications. (C) 1996 Wil
ey-Liss, Inc.