1. ¹Department of Biochemistry, Faculty of Sciences and Technology, University of Coimbra, Apartado 3126, Coimbra, Portugal
2. ²Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
3. ³Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal

Correspondence: Professor MC Pedroso de Lima, Department of Biochemistry, Faculty of Sciences and Technology, University of Coimbra, Apartado 3126, 3001-401 Coimbra, Portugal

Received 11 November 2004; Accepted 9 February 2005; Published online 7 April 2005.

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.