Intranasal Delivery of pGDNF Nanoparticles Results in GDNF Expression Throughout Rat Brain


Glial cell line-derived neurotrophic factor (GDNF) is a potential treatment for various CNS disorders. Gene therapy for GDNF has been investigated as a usefully method to provide a renewable source of GDNF within the brain in an attempt to circumvent the need for repeated dosing. However, the usefulness of GDNF gene therapy has been limited by its inability to cross the blood brain barrier (BBB), and by difficulties in administering it safely via direct intracranial injection of viral vectors, due to immunogenicity of the vector and the invasiveness of surgical intervention. Thus, we are investigating intranasal administration using a non-immunogenic PEGylated polylysine (PEG-CK30) nanoparticle vector developed by Copernicus Therapeutics, Inc. which compacts single expression plasmids. We have previously shown, using a plasmid that expresses both GDNF and enhanced green fluorescent protein (eGFP), that these nanoparticle vectors effectively transfect cells both in vitro and in vivo. æThe goal of this study was to assess in vivo transfection after intranasal administration of compacted GDNF plasmid (pGDNF) nanoparticles in rats. Expression of GDNF throughout the brain was determined 7 days post treatment by ELISA. Results showed significant increases in GDNF expression in a series of rostral-caudal brain slabs. Therefore, intranasal delivery of compacted plasmid-GDNF nanoparticles can be used as an effective approach for gene therapy to treat various CNS disorders.