Herpes Simplex Viral Vectors in Gene Therapy

Abstract

Herpes simplex virus (HSV) is a human pathogen that naturally establishes a life‐long latent infection of human peripheral sensory neurons. Genetically modified recombinant HSV vectors have been constructed that are incapable of replication, but nonetheless efficiently infect and establish a latent‐like state in neurons in vitro and in vivo without the ability to reactivate. These vectors can be used to transfer and express genes in the nervous system using natural expression mechanisms already present in the virus genome. These products are designed to modify the structure and/or function of neuronal elements, and represent a novel therapeutic strategy for diseases of the nervous system.

Keywords: herpes simplex virus (HSV); gene therapy; peripheral neuropathy; pain; Parkinson disease

Figure 1.

Fluorogold‐labelled motor neurons in the ventral horn of the spinal cord 14 days after spinal root avulsion. The lesioned side (right panels) was injected with HSV vectors expressing lacZ, bcl‐2, GDNF, or the bcl‐2 and GDNF vectors in combination. The number of motor neurons surviving at 2 weeks was substantially and significantly increased by vector‐mediated transgene expression (graph). (Reprinted from Natsume A, Mata M, Wolfe D et al. () Bcl‐2 and GDNF delivered by HSV‐mediated gene transfer after spinal root avulsion provide a synergistic effect. Journal of Neurotrauma19: 61–68.)

Figure 2.

Subcutaneous inoculation with an HSV vector expressing neurotrophin‐3 (NT‐3) prevented the loss of evoked sensory response caused by pyridoxine (PDX) overdose (left panels show control, PDX‐intoxicated, PDX‐intoxicated treated with the lacZ‐expressing control vector, and PDX‐intoxicated treated with the NT‐3 expressing HSV vector). The PDX‐intoxicated animals treated with control vector had a severe deficit in proprioception manifest by slipping when attempting to walk on a narrow beam (upper picture), which was prevented in animals inoculated with the NT‐3 expressing vector (lower picture). (From Chattopadhyay M, Wolfe D, Huang S et al. () In vivo gene therapy for pyridoxine‐induced neuropathy by HSV‐mediated gene transfer of neurotrophin‐3. Annals of Neurology51: 19–27.)

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Further Reading

Frampton AR, Jr., Goins WF, Nakano K, Burton EA and Glorioso JC (2005) HSV trafficking and development of gene therapy vectors with applications in the nervous system. Gene Therapy 12: 891–901.

Glorioso JC and Fink DJ (2004) Herpes vector‐mediated gene transfer in treatment of diseases of the nervous system. Annual Review Microbiology 58: 253–271.

Lachmann R (2004) Herpes simplex virus‐based vectors. International Journal of Experimental Pathology 85: 177–190.

Latchman DS (2005) Herpes simplex virus‐based vectors for the treatment of cancer and neurodegenerative disease. Current Opinion Molecular Therapy 7: 415–418.

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How to Cite close
Fink, David J, and Glorioso, Joseph C(Jul 2007) Herpes Simplex Viral Vectors in Gene Therapy. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005739.pub2]