Polyplex gene delivery modulated by redox potential gradients

Polyplexes sensitive to redox potential gradients represent a promising class of vectors for delivery of nucleic acids. This review focuses on the recent advances in the development of these vectors. The biological rationale for the design of redox-sensitive polyplexes is discussed together with the basic synthetic approaches for introducing reducible disulfide bonds into the structure of the polyplexes. The biological properties of the redox-sensitive polyplexes of plasmid DNA, mRNA, antisense oligonucleotides and siRNA are reviewed with emphasis on in vitro cellular delivery, cytotoxicity and in vivo activity. Overall, redox-sensitive polyplexes represent a promising platform for further development as vectors for delivery of a wide variety of therapeutic nucleic acids.