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

Gene Therapy volume 6, pages 994–1005 (1999)Cite this article

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 chol- ine 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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA

    L L Zou & K Yang

  2. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA

    L L Zou & K Yang

  3. Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA, USA

    L Huang

  4. Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX, USA

    R L Hayes, C Black, Y H Qiu & G L Clifton

  5. Department of Human Biochemistry and Genetics, University of Texas Medical Branch at Galveston, Galveston, TX, USA

    J R Perez-Polo

  6. Department of Neurology, Baylor College of Medicine, Houston, TX, USA

    W Le

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Zou, L., Huang, L., Hayes, R. et al. Liposome-mediated NGF gene transfection following neuronal injury: potential therapeutic applications. Gene Ther 6, 994–1005 (1999). https://doi.org/10.1038/sj.gt.3300936

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