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

    55 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 languageEnglish (US)
    Pages (from-to)994-1005
    Number of pages12
    JournalGene Therapy
    Volume6
    Issue number6
    DOIs
    StatePublished - Jun 1 1999

    Keywords

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

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Genetics

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  • Cite this

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