Knocking out insidious genes using RNA-interference (RNAi) has been massively pursued as a therapeutic technique since its discovery. Specifically, methods of delivering RNAi through the blood stream to target tissues have been of great interest. Scientists have successfully packaged and delivered RNAi in lentiviruses, micelles and other nanoparticles. However, the search for cost-effectiveness, efficiency and target accuracy never sleeps (insert wise crack about the tendency of their funding to hibernate).
In a study recently published in Nature Biotechnology, exosomes are suggested to be a significant improvement over other vehicles. The scientists used dendritic cells -- derived from bone marrow progenitor cells, and not to be confused with neural somas -- and proceeded to test the efficiency and accuracy of their RNAi packaging and delivery. They purified the exosomes, tagged them with muscle or brain targeting peptides, loaded them with exogenous cargo (siRNA for GADPH, a housekeeping gene), and tested their delivery both in vitro and in vivo.
Alvarez-Erviti and colleagues achieved a marked knockdown of GADPH in vitro, and an even more impressive knockdown in several peripheral organ and brain region tissues in vivo, suggesting an improved blood brain barrier-transcending capacity compared to other methods. The exosome delivery method was accurate, and achieved a 60% knockdown of mRNA and a 62% knockdown of protein expression using, allegedly, 10% of the siRNA cargo that other methods have used.
62% efficiency is generally accepted as a pretty high yield in the biomedical sciences. Whether this exosomal packing and delivery system can be optimized to better penetrate the blood brain barrier remains to be seen. However, with its cost-effective, accurate and non-invasive methods, the exosome may be the Prius of siRNA delivery.
Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, & Wood MJ (2011). Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nature biotechnology, 29 (4), 341-5 PMID: 21423189