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

doi:10.1016/0169-328X(94)90146-5

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

Neurology

Research output: Contribution to journal › Article › peer-review

59 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 language	English (US)
Pages (from-to)	327-335
Number of pages	9
Journal	Molecular Brain Research
Volume	24
Issue number	1-4
DOIs	https://doi.org/10.1016/0169-328X(94)90146-5
State	Published - Jul 1994

Funding

This work was supported by National Institutes of Health grants (HD27116 to H.J.F.; NS20013 and NS20778 to J.A.K.) and by grants form the American Health Assistance Foundation, the American Paralysis Association, and Alkermes, Inc. (A.I.G.). M.D.G. was supported by the National Institutes of Health Grant GM7288-16. The authors would like to extend their gratitude to Dr. Dominick Sinicropi of Genentech, Inc. for use of the NGF ELISA reagents and the NGF blocking antibody and Drs. Annette Ehrlich, C.J. Chang, and Scott Taber for their statistical assistance.

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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10.1016/0169-328X(94)90146-5

Cite this

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title = "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",

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.",

keywords = "Gene therapy, Gene transfer, Herpes Simplex virus type 1, Nerve growth factor",

author = "Geschwind, {Michael D.} and Kessler, {John A.} and Geller, {Alfred I.} and Federoff, {Howard J.}",

note = "Funding Information: This work was supported by National Institutes of Health grants (HD27116 to H.J.F.; NS20013 and NS20778 to J.A.K.) and by grants form the American Health Assistance Foundation, the American Paralysis Association, and Alkermes, Inc. (A.I.G.). M.D.G. was supported by the National Institutes of Health Grant GM7288-16. The authors would like to extend their gratitude to Dr. Dominick Sinicropi of Genentech, Inc. for use of the NGF ELISA reagents and the NGF blocking antibody and Drs. Annette Ehrlich, C.J. Chang, and Scott Taber for their statistical assistance.",

year = "1994",

month = jul,

doi = "10.1016/0169-328X(94)90146-5",

language = "English (US)",

volume = "24",

pages = "327--335",

journal = "Molecular Brain Research",

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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. / Geschwind, Michael D.; Kessler, John A.; Geller, Alfred I. et al.
In: Molecular Brain Research, Vol. 24, No. 1-4, 07.1994, p. 327-335.

Research output: Contribution to journal › Article › peer-review

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AU - Geschwind, Michael D.

AU - Kessler, John A.

AU - Geller, Alfred I.

AU - Federoff, Howard J.

N1 - Funding Information: This work was supported by National Institutes of Health grants (HD27116 to H.J.F.; NS20013 and NS20778 to J.A.K.) and by grants form the American Health Assistance Foundation, the American Paralysis Association, and Alkermes, Inc. (A.I.G.). M.D.G. was supported by the National Institutes of Health Grant GM7288-16. The authors would like to extend their gratitude to Dr. Dominick Sinicropi of Genentech, Inc. for use of the NGF ELISA reagents and the NGF blocking antibody and Drs. Annette Ehrlich, C.J. Chang, and Scott Taber for their statistical assistance.

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AB - 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.

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KW - Gene transfer

KW - Herpes Simplex virus type 1

KW - Nerve growth factor

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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

Abstract

Funding

Keywords

ASJC Scopus subject areas

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