Transfer of the nerve growth factor gene into cell lines and cultured neurons using a defective Herpes Simplex virus vector. Transfer of the NGF gene into cells by a HSV-1 vector

Michael D. Geschwind, John A. Kessler, Alfred I. Geller, Howard J. Federoff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Nerve growth factor (NGF) can be expressed in cells by gene transfer using a defective Herpes Simplex virus type 1 (HSV-1) vector. In this report, the defective HSV-1 vector, pHSVngf, is used to infect established cell lines and cultured neurons. Infection of cell lines with pHSVngf results in gene transcription, correct RNA processing, and production of biologically active NGF. Infection of the PC12 neuronal cell line results in the production of biologically active NGF and infection of NGF-dependent neonatal sympathetic neurons in primary culture with pHSVngf leads to neuronal survival in the absence of exogenously-added NGF. NGF expressed by pHSVngf-infected cells does not appear to work through an autocrine intracellular pathway since NGF antibody added to culture media of infected cells could block NGF action. Infection with pHSVngf of cholinergic striatal or septal neurons in dissociated cell culture resulted in an increase in choline acetyltransferase activity. These studies demonstrate the efficacy of defective HSV-1 vectors for delivery and expression of neurotrophin genes in cultured neural cells.

Original languageEnglish (US)
Pages (from-to)327-335
Number of pages9
JournalMolecular Brain Research
Volume24
Issue number1-4
DOIs
StatePublished - Jul 1994

Keywords

  • Gene therapy
  • Gene transfer
  • Herpes Simplex virus type 1
  • Nerve growth factor

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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