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Related Experiment Videos

Gene transfer to brain using herpes simplex virus vectors

J C Glorioso1, W F Goins, C A Meaney

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

Annals of Neurology
|January 1, 1994
PubMed
Summary
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Herpes simplex virus type 1 shows promise for gene therapy in the central nervous system. Researchers are developing non-toxic viral vectors for stable, long-term gene expression in neurons.

Area of Science:

  • Neuroscience
  • Virology
  • Gene Therapy

Background:

  • Herpes simplex virus type 1 (HSV-1) infects neurons and can remain latent indefinitely.
  • HSV-1 vectors offer potential for gene transfer to central nervous system (CNS) neurons.
  • Viral gene expression during latency is a key challenge for vector development.

Purpose of the Study:

  • To engineer a non-cytotoxic HSV-1 vector for gene transfer to postmitotic neurons.
  • To identify suitable promoter-regulators for stable foreign gene expression during HSV-1 latency in the CNS.
  • To overcome impediments in using HSV-1 as a gene therapy vehicle.

Main Methods:

  • Engineering a non-cytotoxic HSV-1 mutant by deleting specific immediate early genes.
  • Testing various viral and cellular promoters for gene expression during neuronal latency.

Related Experiment Videos

  • Investigating latency-associated transcript promoters for CNS activity.

    • Main Results:

    • Deletion of immediate early genes renders HSV-1 non-toxic to neurons in vitro and in vivo.
    • HSV-1 vectors enter latency in CNS neurons due to inability to replicate.
    • Latency-associated transcript promoters show low-level but persistent activity in the brain.

    Conclusions:

    • HSV-1 is a viable candidate for gene therapy in the CNS.
    • Further development of promoter-regulators is needed for robust gene expression during latency.
    • Exploiting RNA polymerase III or novel promoters may enhance gene expression in brain neurons.