Localised non-viral delivery of nucleic acids for nerve regeneration in injured nervous systems

Axons damaged by traumatic injuries are often unable to spontaneously regenerate in the adult central nervous system (CNS). Although the peripheral nervous system (PNS) has some regenerative capacity, its ability to regrow remains limited across large lesion gaps due to scar tissue formation. Nucleic acid therapy holds the potential of improving regeneration by enhancing the intrinsic growth ability of neurons and overcoming the inhibitory environment that prevents neurite outgrowth. Nucleic acids modulate gene expression by over-expression of neuronal growth factor or silencing growth-inhibitory molecules. Although in vitro outcomes appear promising, the lack of efficient non-viral nucleic acid delivery methods to the nervous system has limited the application of nucleic acid therapeutics to patients. Here, we review the recent development of efficient non-viral nucleic acid delivery platforms, as applied to the nervous system, including the transfection vectors and carriers used, as well as matrices and scaffolds that are currently used. Additionally, we will discuss possible improvements for localised nucleic acid delivery.