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Gene delivery to rat enteric neurons using herpes simplex virus-based vectors
M K Howard1, R S Coffin, A R Maclean
1Department of Molecular Pathology, University College London Medical School.
Journal of Molecular Neuroscience : MN
|January 4, 1998
Summary
Researchers engineered herpes simplex virus vectors for gene delivery to enteric neurons. Modified viruses efficiently transfer genes to gut neurons for potential central nervous system (CNS) therapies.
Area of Science:
- Neuroscience
- Gene Therapy
- Virology
Background:
- Enteric nervous system (ENS) neurons can be cultured and transplanted into the brain.
- ENS neurons hold potential for delivering therapeutic genes to the central nervous system (CNS).
Purpose of the Study:
- To investigate herpes simplex virus (HSV) vectors for gene delivery to cultured ENS neurons.
- To identify safe and efficient HSV vectors for potential therapeutic applications in the CNS.
Main Methods:
- Cultured ENS neurons were transduced with modified HSV vectors lacking specific viral genes (ICP27, ICP34.5, VMW65).
- Gene delivery efficiency and cellular toxicity were assessed for each vector modification.
Main Results:
- HSV vectors lacking ICP27 efficiently delivered marker genes to ENS neurons with minimal damage.
- Vectors lacking ICP34.5 were inefficient and caused significant cellular damage.
- Vectors lacking both ICP27 and ICP34.5 showed reduced toxicity and efficient gene transfer.
- Inactivation of VMW65 further decreased vector toxicity.
Conclusions:
- HSV vectors, particularly those lacking ICP27 and ICP34.5, represent safe and efficient tools for gene delivery to ENS neurons.
- Engineered ENS neurons could be transplanted into the CNS for therapeutic gene delivery.