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Overcoming barriers in non-viral gene delivery for neurological applications.

Gene therapy for neurological disorders has attracted significant interest as a way to reverse or stop various disease pathologies. Typical gene therapies involving the central and peripheral nervous system make use of adeno-associated viral vectors whose questionable safety and limitations in manufacturing has given rise to extensive research into non-viral vectors. While early research studies have demonstrated limited efficacy with these non-viral vectors, investigation into various vector materials and functionalization methods has provided insight into ways to optimize these non-viral vectors to improve desired characteristics such as improved blood-brain barrier transcytosis, improved perfusion in brain region, enhanced cellular uptake and endosomal escape in neural cells, and nuclear transport of genetic material post- intracellular delivery. Using a combination of various strategies to enhance non-viral vectors, research groups have designed multi-functional vectors that have been successfully used in a variety of pre-clinical applications for the treatment of Parkinson's disease, brain cancers, and cellular reprogramming for neuron replacement. While more work is needed in the design of these multi-functional non-viral vectors for neural applications, much of the groundwork has been done and is reviewed here.