Chapter 7. Advances in Engineering HSV Vectors for Gene Transfer to the Nervous System
- Anthony Meager
Published Online: 10 DEC 2001
DOI: 10.1002/0470842385.ch7
Copyright © 1999 John Wiley & Sons, Ltd
Book Title
Gene Therapy Technologies, Applications and Regulations: From Laboratory to Clinic
Additional Information
How to Cite
Soares, M. K., Goins, W. F., Glorioso, J. C. and Fink, D. J. (2001) Advances in Engineering HSV Vectors for Gene Transfer to the Nervous System, in Gene Therapy Technologies, Applications and Regulations: From Laboratory to Clinic (ed A. Meager), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/0470842385.ch7
Editor Information
Division of Immunobiology, The National Institute for Biological Standards and Control, South Mimms, UK
Publication History
- Published Online: 10 DEC 2001
- Published Print: 17 SEP 1999
ISBN Information
Print ISBN: 9780471967095
Online ISBN: 9780470842386
- Summary
- Chapter
Keywords:
- herpes simplex virus;
- neurological disease;
- latency;
- capacity;
- cytotoxicity;
- amplicon;
- adeno-associated virus;
- hybrid vector;
- vector engineering
Summary
Neurological diseases considered amenable to gene therapy include neurodegenerative disorders, brain tumours and autoimmune defects that lead to the destruction of nerve tissue. Herpes simplex virus (HSV) establishes long-term latency in neurons, evading immune surveillance while continuing to express latency-associated transcripts, making it an attractive candidate vector. Engineered improvements in the virus to facilitate gene therapy embrace deletion of accessory functions to increase the capacity for foreign genes, deletion of genes associated with cytotoxicity and the use of promoters to drive either transient or long-term expression of the transgene, both constitutively and inducibly. Amplicons are plasmids engineered to contain an HSV origin of replication and packaging signals as well as a bacterial origin of replication. These are co-transfected with a defective HSV helper virus and have been tested as gene transfer vectors in animal systems but toxicity remains a problem. Hybrid HSV-adeno-associated virus vectors have also been engineered.