Synthetic small interfering RNAs (siRNAs) are potent inhibitors of gene expression through the RNA interference mechanism. The therapeutic potential of RNAi will be fully realized when these agents can be efficiently delivered into the cells of specific organs or tissues. At Alnylam, we have developed a three-pronged approach to enable efficient delivery of siRNAs into liver hepatocytes after either intravenous or subcutaneous injection. These methods include chemical modification of siRNAs, lipid nanoparticle formulation of siRNAs, and multivalent <i>N</i>-acetylgalactosamine (GalNAc) conjugation to siRNAs. Now, the potential of siRNA in treatment of “undruggable” diseases that was envisioned by the researchers is being realized. There are now several siRNA-based drugs in various stages of clinical testing and successful clinical results are emerging from these trials. The strategies and results will be discussed.

Delivery of chemically modified siRNAs for human therapeutics: From principles to patients

256th National Meeting (2018)

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