Infection of cultured striatal neurons with a defective HSV-1 vector: implications for gene therapy.
Several neurological diseases which affect the corpus striatum are candidates for gene therapy. We have developed a defective Herpes Simplex Virus (HSV-1) vector system to introduce genes into postmitotic cells, such as neurons. The prototype vector, pHSVlac, contains a transcription unit which places the E. coli Lac Z gene under the control of the HSV-1 immediate early (IE) 4/5 promoter, a constitutive promoter. We now demonstrate that a HSV-1 vector can deliver a gene into striatal neurons. Infection of cultured rat striatal neurons with pHSVlac virus resulted in stable expression of beta-galactosidase for at least two weeks, without cell death. The potential to replace the Lac Z gene with other genes of interest, such as the gene responsible for Huntington's Disease, once it is isolated, may lead to insights about the pathogenesis of this genetic neurodegenerative disease, and may provide a method for performing gene therapy on this disease. Similarly, introduction of the tyrosine hydroxylase gene, which encodes the rate-limiting enzyme in the conversion of tyrosine to dopamine, into striatal neurons might provide a novel gene therapy approach towards treating Parkinson's Disease.
Freese
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Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139.
Geller
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D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology; D003673:Defective Viruses / Q000235:genetics*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D000882:Haplorhini; D007763:Lac Operon; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000382:microbiology*; D010957:Plasmids / Q000235:genetics; D051381:Rats; D018139:Simplexvirus / Q000235:genetics*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D001616:beta-Galactosidase