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Tf-lipoplex-mediated NGF gene transfer to the CNS: neuronal protection and recovery in an excitotoxic model of brain injury

Gene Therapy volume 12, pages 1242–1252 (2005)Cite this article

Abstract

The development of efficient systems for in vivo gene transfer to the central nervous system (CNS) may provide a useful therapeutic strategy for the alleviation of several neurological disorders. In this study, we evaluated the feasibility of nonviral gene therapy to the CNS mediated by cationic liposomes. We present evidence of the successful delivery and expression of both a reporter and a therapeutic gene in the rodent brain, as evaluated by immunohistochemical assays. Our results indicate that transferrin-associated cationic liposome/DNA complexes (Tf-lipoplexes) allow a significant enhancement of transfection activity as compared to plain complexes, and that 8/1 (+/−) Tf-lipoplexes constitute the best formulation to mediate in vivo gene transfer. We demonstrated that Tf-lipoplex-mediated nerve growth factor transgene expression attenuates the morphological damages of the kainic acid-induced lesion as assessed by 2,3,5-triphenyltetrazolium chloride (TTC) vital staining. These findings suggest the usefulness of these lipid-based vectors in mediating the delivery of therapeutic genes to the CNS.

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Acknowledgements

We thank Professor Patrick Aebischer, Institut des Neurosciences, École Polytechnique de Lausanne, Lausanne, Switzerland, for providing the pSIN-PGK-nls-LacZ-WHV plasmid, and Dr Robert Debs, California Pacific Medical Center Research Institute, San Francisco, USA, for the pCMV-NGF plasmid generous gift. We are grateful to Professor Tice Macedo and to Frederico Pereira for providing access to the stereotactic frame used throughout this study. M Teresa Girão da Cruz was the recipient of a fellowship from the Portuguese Foundation for Science and Technology (PRAXIS XXI/BD/19529/99). This work was partially financed by a grant from the Portuguese Foundation for Science and Technology (FCT/BIO/36202/00).

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Sciences and Technology, University of Coimbra, Apartado 3126, Coimbra, Portugal

    M Teresa Girão da Cruz, A L C Cardoso & M C Pedroso de Lima

  2. Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    M Teresa Girão da Cruz, A L C Cardoso, L P de Almeida, S Simões & M C Pedroso de Lima

  3. Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal

    L P de Almeida & S Simões

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Teresa Girão da Cruz, M., Cardoso, A., de Almeida, L. et al. Tf-lipoplex-mediated NGF gene transfer to the CNS: neuronal protection and recovery in an excitotoxic model of brain injury. Gene Ther 12, 1242–1252 (2005). https://doi.org/10.1038/sj.gt.3302516

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