Delivery materials for siRNA therapeutics

Therapeutics based on small interfering RNA (siRNA), which in principle are able to reversibly silence any gene of interest, are under development for the treatment of cancers, viral infections, hereditary disorders and many other diseases. This Review discusses the biological challenges that siRNA delivery materials aim to overcome, as well as the most clinically advanced classes of siRNA delivery systems, including cyclodextrin–polymer nanoparticles, lipid nanoparticles and siRNA conjugates. RNA interference (RNAi) has broad potential as a therapeutic to reversibly silence any gene. To achieve the clinical potential of RNAi, delivery materials are required to transport short interfering RNA (siRNA) to the site of action in the cells of target tissues. This Review provides an introduction to the biological challenges that siRNA delivery materials aim to overcome, as well as a discussion of the way that the most effective and clinically advanced classes of siRNA delivery systems, including lipid nanoparticles and siRNA conjugates, are designed to surmount these challenges. The systems that we discuss are diverse in their approaches to the delivery problem, and provide valuable insight to guide the design of future siRNA delivery materials.