Liposome-mediated NGF gene transfection following neuronal injury: Potential therapeutic applications

L. L. Zou; L. Huang; R. L. Hayes; C. Black; Y. H. Qiu; J. R. Perez-Polo; W. Le; G. L. Clifton; K. Yang

doi:10.1038/sj.gt.3300936

Liposome-mediated NGF gene transfection following neuronal injury: Potential therapeutic applications

L. L. Zou, L. Huang, R. L. Hayes, C. Black, Y. H. Qiu, J. R. Perez-Polo, W. Le, G. L. Clifton, K. Yang

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

58 Scopus citations

Abstract

We have systematically investigated the therapeutic potential of cationic liposome-mediated neurotrophic gene transfer for treatment of CNS injury. Following determination of optimal transfection conditions, we examined the effects of dimethylaminoethane-carbamoyl-cholesterol (DC-Chol) liposome-mediated NGF cDNA transfection in injured and uninjured primary septo-hippocampal cell cultures and rat brains. In in vitro studies, we detected an increase of NGF mRNA in cultures 1 day after transfection. Subsequent ELISA and PC12 cell biological assays confirmed that cultured cells secreted soluble active NGF into the media from day 2 after gene transfection. Further experiments showed that such NGF gene transfection reduced the loss of choline acetyltransferase (ChAT) activity in cultures following calcium-dependent depolarization injury. In in vivo studies, following intraventricular injections of NGF cDNA complexed with DC-Chol liposomes, ELISA detected nine- to 12-fold increases of NGF in rat CSF. Further studies showed that liposome/NGF cDNA complexes could attenuate the loss of cholinergic neuronal immunostaining in the rat septum after traumatic brain injury (TBI). Since deficits in cholinergic neurotransmission are a major consequence of TBI, our studies demonstrate for the first time that DC-Chol liposome-mediated NGF gene transfection may have therapeutic potential for treatment of brain injury.

Original language	English (US)
Pages (from-to)	994-1005
Number of pages	12
Journal	Gene Therapy
Volume	6
Issue number	6
DOIs	https://doi.org/10.1038/sj.gt.3300936
State	Published - Jun 1999

Keywords

CNS
ChAT
Gene therapy
Liposomes
NGF
Neuronal injury

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics

Access to Document

10.1038/sj.gt.3300936

Cite this

@article{304dee1430414aad8ef8159a43e9f52a,

title = "Liposome-mediated NGF gene transfection following neuronal injury: Potential therapeutic applications",

abstract = "We have systematically investigated the therapeutic potential of cationic liposome-mediated neurotrophic gene transfer for treatment of CNS injury. Following determination of optimal transfection conditions, we examined the effects of dimethylaminoethane-carbamoyl-cholesterol (DC-Chol) liposome-mediated NGF cDNA transfection in injured and uninjured primary septo-hippocampal cell cultures and rat brains. In in vitro studies, we detected an increase of NGF mRNA in cultures 1 day after transfection. Subsequent ELISA and PC12 cell biological assays confirmed that cultured cells secreted soluble active NGF into the media from day 2 after gene transfection. Further experiments showed that such NGF gene transfection reduced the loss of choline acetyltransferase (ChAT) activity in cultures following calcium-dependent depolarization injury. In in vivo studies, following intraventricular injections of NGF cDNA complexed with DC-Chol liposomes, ELISA detected nine- to 12-fold increases of NGF in rat CSF. Further studies showed that liposome/NGF cDNA complexes could attenuate the loss of cholinergic neuronal immunostaining in the rat septum after traumatic brain injury (TBI). Since deficits in cholinergic neurotransmission are a major consequence of TBI, our studies demonstrate for the first time that DC-Chol liposome-mediated NGF gene transfection may have therapeutic potential for treatment of brain injury.",

keywords = "CNS, ChAT, Gene therapy, Liposomes, NGF, Neuronal injury",

author = "Zou, {L. L.} and L. Huang and Hayes, {R. L.} and C. Black and Qiu, {Y. H.} and Perez-Polo, {J. R.} and W. Le and Clifton, {G. L.} and K. Yang",

note = "Funding Information: This work was supported by grants from the National Institutes of Health, RO1-NS35502 to K Yang, CA 64654 to L Huang and RO1-NS21458 to R Hayes. Texas Higher Education Coordinating Board grants ARP 011618–100 and ATP 004949–049 to K Yang and the Vivian L Smith Center for Neurologic Research.",

year = "1999",

month = jun,

doi = "10.1038/sj.gt.3300936",

language = "English (US)",

volume = "6",

pages = "994--1005",

journal = "Gene Therapy",

issn = "0969-7128",

publisher = "Nature Publishing Group",

number = "6",

}

TY - JOUR

T1 - Liposome-mediated NGF gene transfection following neuronal injury

T2 - Potential therapeutic applications

AU - Zou, L. L.

AU - Huang, L.

AU - Hayes, R. L.

AU - Black, C.

AU - Qiu, Y. H.

AU - Perez-Polo, J. R.

AU - Le, W.

AU - Clifton, G. L.

AU - Yang, K.

N1 - Funding Information: This work was supported by grants from the National Institutes of Health, RO1-NS35502 to K Yang, CA 64654 to L Huang and RO1-NS21458 to R Hayes. Texas Higher Education Coordinating Board grants ARP 011618–100 and ATP 004949–049 to K Yang and the Vivian L Smith Center for Neurologic Research.

PY - 1999/6

Y1 - 1999/6

N2 - We have systematically investigated the therapeutic potential of cationic liposome-mediated neurotrophic gene transfer for treatment of CNS injury. Following determination of optimal transfection conditions, we examined the effects of dimethylaminoethane-carbamoyl-cholesterol (DC-Chol) liposome-mediated NGF cDNA transfection in injured and uninjured primary septo-hippocampal cell cultures and rat brains. In in vitro studies, we detected an increase of NGF mRNA in cultures 1 day after transfection. Subsequent ELISA and PC12 cell biological assays confirmed that cultured cells secreted soluble active NGF into the media from day 2 after gene transfection. Further experiments showed that such NGF gene transfection reduced the loss of choline acetyltransferase (ChAT) activity in cultures following calcium-dependent depolarization injury. In in vivo studies, following intraventricular injections of NGF cDNA complexed with DC-Chol liposomes, ELISA detected nine- to 12-fold increases of NGF in rat CSF. Further studies showed that liposome/NGF cDNA complexes could attenuate the loss of cholinergic neuronal immunostaining in the rat septum after traumatic brain injury (TBI). Since deficits in cholinergic neurotransmission are a major consequence of TBI, our studies demonstrate for the first time that DC-Chol liposome-mediated NGF gene transfection may have therapeutic potential for treatment of brain injury.

AB - We have systematically investigated the therapeutic potential of cationic liposome-mediated neurotrophic gene transfer for treatment of CNS injury. Following determination of optimal transfection conditions, we examined the effects of dimethylaminoethane-carbamoyl-cholesterol (DC-Chol) liposome-mediated NGF cDNA transfection in injured and uninjured primary septo-hippocampal cell cultures and rat brains. In in vitro studies, we detected an increase of NGF mRNA in cultures 1 day after transfection. Subsequent ELISA and PC12 cell biological assays confirmed that cultured cells secreted soluble active NGF into the media from day 2 after gene transfection. Further experiments showed that such NGF gene transfection reduced the loss of choline acetyltransferase (ChAT) activity in cultures following calcium-dependent depolarization injury. In in vivo studies, following intraventricular injections of NGF cDNA complexed with DC-Chol liposomes, ELISA detected nine- to 12-fold increases of NGF in rat CSF. Further studies showed that liposome/NGF cDNA complexes could attenuate the loss of cholinergic neuronal immunostaining in the rat septum after traumatic brain injury (TBI). Since deficits in cholinergic neurotransmission are a major consequence of TBI, our studies demonstrate for the first time that DC-Chol liposome-mediated NGF gene transfection may have therapeutic potential for treatment of brain injury.

KW - CNS

KW - ChAT

KW - Gene therapy

KW - Liposomes

KW - NGF

KW - Neuronal injury

UR - http://www.scopus.com/inward/record.url?scp=0033020604&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033020604&partnerID=8YFLogxK

U2 - 10.1038/sj.gt.3300936

DO - 10.1038/sj.gt.3300936

M3 - Article

C2 - 10455401

AN - SCOPUS:0033020604

SN - 0969-7128

VL - 6

SP - 994

EP - 1005

JO - Gene Therapy

JF - Gene Therapy

IS - 6

ER -

Liposome-mediated NGF gene transfection following neuronal injury: Potential therapeutic applications

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this