Bioresponsive polymers for nonviral gene delivery

Gene therapy is attracting increasing attention because of its potential for therapeutic interventions in cancer and other diseases. Nonviral gene vectors have been used for more than three decades, and the development of novel carriers with decreased cytotoxicity, improved delivery and enhanced transfection efficiency has remained an important aim. By structural alterations such as conformational changes or chemical bond cleavage, bioresponsive polycations can improve the transfection properties of polyplexes--formed by cationic polymers to deliver nucleic acids into cells--at various steps of delivery. These polycations can respond to subtle differences between the extracellular and intracellular environments. Along with noncovalently formed polyplexes, the development of covalent polymer-oligonucleotide conjugates with bioresponsive linkers is promising as nucleic acid therapeutics.