Progress toward developing an intranasal gene therapy approach for CNS disorders

Delivery of genes encoding therapeutic proteins has potential for treatment of neurodegenerative disorders of the brain. Most studies have used intracerebral injections of viral vectors to achieve CNS transfection. However, safety concerns including invasive surgical methods to introduce the gene to target brain areas decrease clinical applicability of this approach. We have shown successful delivery of neurotrophic proteins to the brain via the intranasal route of administration, which bypasses the blood‐brain barrier and avoids systemic absorption. The focus of this work is to determine whether this route can also be utilized for non‐viral CNS gene therapy. Copernicus Therapeutics has developed a non‐viral DNA nanoparticle delivery technology in which single molecules of DNA are compacted with polycations, such as polyethylene‐glycol substituted lysine 30‐mers (PEG‐CK30), formulating nanorods of 8–11 nm. These nanoparticles are non‐immunogenic, non‐inflammatory and can deliver genes to post‐mitotic cells in the brain. In our studies, rats were intranasally administered reporter pDNA compacted with PEG‐CK30, sacrificed, and their brains analyzed for protein expression using ELISA and immunohistochemistry. Achieving successful transfection in rat brain provides proof of principle that intranasal delivery can be used for neurotrophic protein expression aimed at treatment of CNS disorders.