DNA and RNA delivery to the lungs using polymers

In recent years genetic modification of cells has promised to revolutionize medicine by offering novel therapeutic approaches in a range of diseases. However, lack of effective means of delivery has so far limited therapeutic applications. Polymeric vectors have been a much-investigated area of non-viral gene delivery but until recently the focus has been on plasmid DNA (pDNA) delivery. Current research suggests that polymer-mediated siRNA delivery is gaining momentum. Previous work in our group has resulted in an effective non-cytotoxic alternative to PEI for pDNA delivery in the lungs, using the reductive environment of the cytoplasm as a means of triggering polymer degradation. Here we present a review covering delivery of either pDNA or siRNA to the lungs, using different polymers. We critically review the key structural polymer characteristics for efficient gene lung delivery. We conclude that for highly efficient pulmonary gene delivery, non-toxic, bioresponsive polymers are required transfer the nucleic acid and genetically modify the lung tissue.