According to Professor Ron Breslow, “biomimetic chemistry” is new chemistry inspired by the principles used by Nature. Synthetic small interfering RNAs (siRNAs) are potent inhibitors of gene expression. These molecules are perfect examples of biomimetic chemistry as synthetic siRNAs act through the natural RNA interference (RNAi) pathway. To deliver therapeutic siRNAs into human liver, we developed approaches that include chemical modification of the siRNAs and either lipid nanoparticle (LNP) formulation or multivalent N-acetylgalactosamine (GalNAc) conjugation, making possible intravenous and subcutaneous administration, respectively. The design of chemical modifications of siRNAs to enable favorable Argonaute2 (Ago2) recognition as well as both delivery strategies rely on biomimetics. The LNP approach is based on the endogenous Apo-E ligand /LDL receptor process. Using these strategies five approved RNAi therapeutics have emerged from Alnylam. This presentation will cover the molecular basis of RNA therapeutics including the chemical modifications and motifs used in each RNA strand to ensure uptake into cells of the targeted tissue, Ago2 recognition, silencing efficiency, metabolic stability, and safety.