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HSV as a gene transfer vector for the nervous system

J C Glorioso1, M A Bender, W F Goins

  • 1Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, PA 15261, USA.

Molecular Biotechnology
|August 1, 1995
PubMed
Summary

Gene therapy for neurological disorders needs effective vectors. Replication-defective Herpes Simplex Virus (HSV) vectors show promise for delivering genes into non-dividing nerve cells, enabling sustained therapeutic expression.

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Area of Science:

  • Neuroscience
  • Gene Therapy
  • Virology

Background:

  • Gene therapy for nervous system diseases necessitates vectors targeting postmitotic cells.
  • Herpes simplex virus type 1 (HSV) is a neurotropic virus that naturally infects neurons and establishes latency.

Purpose of the Study:

  • To evaluate replication-defective HSV vectors for gene delivery in the nervous system.
  • To explore strategies for achieving transient and long-term transgene expression using HSV vectors.

Main Methods:

  • Development of replication-defective HSV vectors with deletions in essential immediate early genes.
  • Utilizing HSV vectors for gene delivery into neural tissues.
  • Exploiting natural viral latency promoters for transgene expression.

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Main Results:

  • Replication-defective HSV vectors are less cytotoxic and capable of establishing latency.
  • Vigorous, transient expression of foreign genes achieved in brain and other tissues.
  • Long-term, albeit weak, foreign gene expression demonstrated in the nervous system.

Conclusions:

  • Replication-defective HSV vectors are viable tools for gene therapy in the nervous system.
  • Exploiting latency-associated promoters can achieve sustained transgene expression.
  • Further research is needed to design optimized latency-based promoter systems for specific gene therapy applications.