Strategies and materials of SMARTnon-viral vectors: Overcoming the barriers for brain gene therapy

Most brain diseases such as tumors and neurodegenerative diseases are devastating for patients with high morbidity and mortality. Gene therapy is a promising strategy for the treatment of brain diseases. The widespread use of brain gene therapy requires the development of safe and effective non-viral vectors as its efficiency is seriously limited due to the instability, unfavorable biodistribution, and poor cellular uptake of genetic drugs. It is required that non-viral vectors should deliver the genetic drugs into brain and further into their action site of specific cells to enhance the therapeutic efficacy and minimize the nonspecific toxicity. However, it poses major challenges to non-viral vectors as there are many transport hurdles existing for brain gene therapy. These tissue and cellular hurdles mainly include blood-brain barrier, nonspecific cellular uptake, endosome trapping, and invasive monitoring. In this review, it provides an overview of the non-viral vectors used for brain gene therapy, and discusses the strategies and materials that have been developed for SMARTnon-viral vectors to overcome these barriers for brain gene therapy. The review discusses the potential of translation for SMARTnon-viral vectors to the clinic. Furthermore, the review provides an outlook for this field. (C) 2020 Elsevier Ltd. All rights reserved.