The ability to specifically silence genes using RNA interference (RNAi) has wide therapeutic applications for the treatment
of disease or the augmentation of tissue formation. RNAi is the sequence‐specific gene silencing mediated by a 21–25 nucleotide
double‐stranded small interfering RNA (siRNA) molecule. siRNAs are incorporated into the RNA‐induced silencing complex (RISC),
which mediates mRNA sequence‐specific binding and cleavage. Although RNAi has the potential to be a powerful therapeutic drug,
its delivery remains a major limitation. The generation of nanosized particles is being investigated to enhance the delivery
of siRNA‐based drugs. These nanoparticles are generally designed to overcome one or more of the barriers encountered by the
siRNA when trafficked to the cytosol. In this review, we will discuss recent advances in the design of delivery strategies
for siRNA, focusing our attention to those strategies that have had in vivo success or have introduced novel functionality that allowed enhanced intracellular trafficking and/or cellular targeting.
First, we will discuss the different barriers that must be overcome for efficient siRNA delivery. Second, we will discuss
the approaches for siRNA delivery by size including direct modification of siRNAs (less than 10 nm), self‐assembled particles
based on cationic polymers and cationic lipids (100‐300 nm), neutral liposomes (<200 nm), and macroscale matrices that contain
naked siRNA or siRNA loaded nanoparticles (>100 µm). Finally, we will briefly discuss recent in vivo therapeutic success. WIREs Nanomed Nanobiotechnol 2010 2 305–315
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Schematic of the limitations to small interfering RNA (siRNA) delivery and the siRNA‐induced RNAi pathway. Limitations to siRNA delivery include: (A) siRNA stability, (B) siRNA nanoparticle stability, (C) siRNA or siRNA nanoparticle targeting and internalization, (D) siRNA endosomal escape, and (E) siRNA off‐target effects.
works at the interface of biotechnology and materials science. His lab is researching many topics, such as investigating the mechanism of release from polymeric delivery systems with concomitant microstructural analysis and mathematical modeling; studying applications of these systems including the development of effective long-term delivery systems for insulin, anti-cancer drugs, growth factors, gene therapy agents and vaccines; developing controlled release systems that can be magnetically, ultrasonically, or enzymatically triggered to increase release rates; synthesizing new biodegradable polymeric delivery systems which will ultimately be absorbed by the body; creating new approaches for delivering drugs such as proteins and genes across complex barriers such as the blood-brain barrier, the intestine, the lung and the skin; stem cell research including controlling growth and differentiation; and creating new biomaterials with shape memory or surface switching properties.