The use of herpes simplex virus-based vectors for gene delivery to the nervous system

1997 ◽  
Vol 3 (9) ◽  
pp. 404-411 ◽  
Author(s):  
Robin H. Lachmann ◽  
Stacey Efstathiou
Keyword(s):  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Gene Delivery ◽  
Simplex Virus

Herpes Simplex Virus as a Gene-Delivery Vector for the Central Nervous System

Viral Vectors ◽  
1995 ◽  
pp. 1-23 ◽  
Author(s):  
Joseph C. Glorioso ◽  
Mary Ann Bender ◽  
William F. Goins ◽  
Neal DeLuca ◽  
David J. Fink
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Gene Delivery ◽  
Gene Delivery Vector ◽  
Delivery Vector ◽  
The Central Nervous System ◽  
Simplex Virus

scholarly journals Development and Optimization of Herpes Simplex Virus Vectors for Multiple Long-Term Gene Delivery to the Peripheral Nervous System

2000 ◽  
Vol 74 (12) ◽  
pp. 5604-5618 ◽  
Author(s):  
J. A. Palmer ◽  
R. H. Branston ◽  
C. E. Lilley ◽  
M. J. Robinson ◽  
F. Groutsi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Gene Delivery ◽  
Active Region ◽  
Spinal Ganglia ◽  
Efficient Gene ◽  
Simplex Virus

ABSTRACT Herpes simplex virus (HSV) has often been suggested as a suitable vector for gene delivery to the peripheral nervous system as it naturally infects sensory nerve terminals before retrograde transport to the cell body in the spinal ganglia where latency is established. HSV vectors might therefore be particularly appropriate for the study and treatment of chronic pain following vector administration by relatively noninvasive peripheral routes. However parameters allowing safe and efficient gene delivery to spinal ganglia following peripheral vector inoculation, or the long-term expression of delivered genes, have not been comprehensively studied. We have identified combinations of deletions from the HSV genome which allow highly efficient gene delivery to spinal dorsal root ganglia (DRGs) following either footpad or sciatic nerve injection. These vectors have ICP34.5 deleted and have inactivating mutations in vmw65. We also report that peripheral replication is probably necessary for the efficient establishment of latency in vivo, as fully replication-incompetent HSV vectors allow efficient gene expression in DRGs only after peripheral inoculation at a high virus dose. Very low transduction efficiencies are otherwise achieved. In parallel, promoters have been developed that allow the long-term expression of individual or pairs of genes in DRGs by using elements from the latently active region of the virus to confer a long-term activity onto a number of promoters which otherwise function only in the short term. This work further defines elements and mechanisms within the latently active region that are necessary for long-term gene expression and for the first time allows multiple inserted genes to be expressed from HSV vectors during latency.

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