Brain-Targeted Polymers for Gene Delivery in the Treatment of Brain Diseases

Abstract

Gene therapies have become a promising strategy for treating neurological disorders, such as brain cancer and neurodegenerative diseases, with the help of molecular biology interpreting the underlying pathological mechanisms. Successful cellular manipulation against these diseases requires efficient delivery of nucleic acids into brain and further into specific neurons or cancer cells. Compared with viral vectors, non-viral polymeric carriers provide a safer and more flexible way of gene delivery, although suffering from significantly lower transfection efficiency. Researchers have been devoted to solving this defect, which is attributed to the multiple barriers existing for gene therapeutics in vivo, such as systemic degradation, blood–brain barrier, and endosome trapping. This review will be mainly focused on systemically administrated brain-targeted polymers developed so far, including PEI, dendrimers, and synthetic polymers with various functions. We will discuss in detail how they are designed to overcome these barriers and how they efficiently deliver therapeutic nucleic acids into targeted cells.