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 journalArticle

    54 Citations (Scopus)

    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 languageEnglish (US)
    Pages (from-to)994-1005
    Number of pages12
    JournalGene Therapy
    Volume6
    Issue number6
    DOIs
    StatePublished - Jun 1999

    Fingerprint

    Nerve Growth Factor
    Liposomes
    Transfection
    Wounds and Injuries
    Genes
    Complementary DNA
    Cholesterol
    Therapeutics
    Cholinergic Agents
    Enzyme-Linked Immunosorbent Assay
    Intraventricular Injections
    Choline O-Acetyltransferase
    PC12 Cells
    Synaptic Transmission
    Biological Assay
    Brain Injuries
    Cultured Cells
    Cell Culture Techniques
    Calcium
    Messenger RNA

    Keywords

    • ChAT
    • CNS
    • Gene therapy
    • Liposomes
    • Neuronal injury
    • NGF

    ASJC Scopus subject areas

    • Genetics

    Cite this

    Zou, L. L., Huang, L., Hayes, R. L., Black, C., Qiu, Y. H., Perez-Polo, J. R., ... Yang, K. (1999). Liposome-mediated NGF gene transfection following neuronal injury: Potential therapeutic applications. Gene Therapy, 6(6), 994-1005. https://doi.org/10.1038/sj.gt.3300936

    Liposome-mediated NGF gene transfection following neuronal injury : Potential therapeutic applications. / Zou, L. L.; Huang, L.; Hayes, R. L.; Black, C.; Qiu, Y. H.; Perez-Polo, J. R.; Le, W.; Clifton, G. L.; Yang, K.

    In: Gene Therapy, Vol. 6, No. 6, 06.1999, p. 994-1005.

    Research output: Contribution to journalArticle

    Zou, LL, Huang, L, Hayes, RL, Black, C, Qiu, YH, Perez-Polo, JR, Le, W, Clifton, GL & Yang, K 1999, 'Liposome-mediated NGF gene transfection following neuronal injury: Potential therapeutic applications', Gene Therapy, vol. 6, no. 6, pp. 994-1005. https://doi.org/10.1038/sj.gt.3300936
    Zou, L. L. ; Huang, L. ; Hayes, R. L. ; Black, C. ; Qiu, Y. H. ; Perez-Polo, J. R. ; Le, W. ; Clifton, G. L. ; Yang, K. / Liposome-mediated NGF gene transfection following neuronal injury : Potential therapeutic applications. In: Gene Therapy. 1999 ; Vol. 6, No. 6. pp. 994-1005.
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