Gene therapy has emerged as a potential new approach to treat genetic disorders by delivering therapeutic genes to target diseased tissues. However, its clinical use has been impeded by gene delivery systems. The viral vectors are very efficient in delivering and expressing their carried genes, but they have safety issues in clinical use. While nonviral vectors are much safer with very low risks after careful material design, but their gene transcription efficiency is too low to be clinically used. Thus, rational design of nonviral vectors mimicking the viral vectors would be a way to break this bottleneck. This review compares side-by-side how viral/nonviral gene vectors transcend these biological barriers in terms of blood circulation, cellular uptake, endosome escape, nucleus import and gene transcription.
