CHAPTER 17: Cationic Polymers in the Central Nervous System: Past, Present and Future

Gene therapy has immense potential to manage the burden of neurological problems. Gene therapy to the central nervous system can be accomplished either by using a viral or a non-viral vector. Non-viral vectors are superior to viral vectors in terms of their safety profiles. However, their significantly low transfection efficiency is a major concern in the development of sustained non-viral gene therapy to the brain. The post-mitotic nature of neurons and the ability of non-viral vectors to cross the blood–brain barrier are the two challenging tasks that have yet to be addressed. Here, in this review, we have summarized the list of cationic polymers used for gene delivery to the brain and associated challenges. Cationic polymers are positively charged molecules that have a ready affinity towards negatively charged DNA/RNA, which allows them to carry genes. Cationic polymers are good candidates for gene therapy in the brain; however, there is scope for improvement to make them better. Development of newer synthetic cationic polymers and modification of natural polymers is the future for brain gene delivery. A biomaterials approach will also help to improve gene therapy. Biomaterial scaffolds can provide gene delivery with a safe degradation profile as well as a depot system that will allow long-term therapeutic effects. Sustained gene therapy in the brain can be achieved by integration of efforts from biology, technology, engineering and nanotechnology.