Gene therapy harbors great promise for the treatment of a variety of inherited and acquired diseases, but its potential can be realized only with safe and effective carriers. Although viruses can efficiently transfer foreign genes to cells, their long-term safety remains a concern. Polymers can serve as a carrier to facilitate gene transfer, either by condensing DNA to the size of nanoparticles that can be internalized by cells, or by entrapping DNA in matrices or micro/nanoparticles for sustained release. However, polymeric controlled gene delivery remains highly inefficient. This review covers the major barriers for nonviral gene transfer and briefly describes the different types of polymers developed to overcome these barriers. With the tremendous promise of genetic medicine, nonviral gene delivery is a worthy goal for biomaterials and nanotechnology research.
