RNA interference (RNAi) therapeutics have emerged as a novel class of drugs capable of treating diseases by targeting gene expression at the posttranscriptional level. As of May 2024, six RNAi-based therapeutics have been approved by the FDA, including nedosiran, the most recently approved one. These therapeutics primarily target the 3' untranslated regions (3'UTRs) of target mRNAs, similar to microRNAs (miRNAs), and some induce mRNA degradation through near-complete base-pair complementarity. This blurs the distinction between siRNAs and miRNAs, suggesting a unified nomenclature of "RNAi" therapeutics aligns better with current pharmacological criteria. The six FDA-approved siRNA therapeutics include patisiran, lumasiran, inclisiran, vutrisiran, givosiran, and nedosiran. They all utilize RNAi mechanisms to regulate gene expression, with some targeting the 3'UTR and others the coding sequence (CDS). These therapeutics are delivered using lipid nanoparticles (LNPs) or conjugated with ligands like GalNAc to enhance tissue targeting. The chemistry of these therapeutics involves extensive modifications to enhance stability and specificity. These therapeutics are used to treat various diseases, including hereditary transthyretin-mediated amyloidosis, primary hyperoxaluria type 1, and heterozygous familial hypercholesterolemia. They demonstrate significant efficacy in reducing disease-related proteins and biomarkers, with some showing sustained reductions over extended periods. The growing number of RNAi therapeutics highlights the need for a unified nomenclature that reflects their pharmacological action rather than their chemistry or sequence complementarity. The term "RNAi therapeutics" encompasses both siRNAs and miRNAs, aligning with current pharmacological criteria and supporting the development of broader RNAi therapies. This unified approach facilitates clearer communication among researchers, clinicians, and educators, ensuring accurate and comprehensive naming of therapeutic agents.RNA interference (RNAi) therapeutics have emerged as a novel class of drugs capable of treating diseases by targeting gene expression at the posttranscriptional level. As of May 2024, six RNAi-based therapeutics have been approved by the FDA, including nedosiran, the most recently approved one. These therapeutics primarily target the 3' untranslated regions (3'UTRs) of target mRNAs, similar to microRNAs (miRNAs), and some induce mRNA degradation through near-complete base-pair complementarity. This blurs the distinction between siRNAs and miRNAs, suggesting a unified nomenclature of "RNAi" therapeutics aligns better with current pharmacological criteria. The six FDA-approved siRNA therapeutics include patisiran, lumasiran, inclisiran, vutrisiran, givosiran, and nedosiran. They all utilize RNAi mechanisms to regulate gene expression, with some targeting the 3'UTR and others the coding sequence (CDS). These therapeutics are delivered using lipid nanoparticles (LNPs) or conjugated with ligands like GalNAc to enhance tissue targeting. The chemistry of these therapeutics involves extensive modifications to enhance stability and specificity. These therapeutics are used to treat various diseases, including hereditary transthyretin-mediated amyloidosis, primary hyperoxaluria type 1, and heterozygous familial hypercholesterolemia. They demonstrate significant efficacy in reducing disease-related proteins and biomarkers, with some showing sustained reductions over extended periods. The growing number of RNAi therapeutics highlights the need for a unified nomenclature that reflects their pharmacological action rather than their chemistry or sequence complementarity. The term "RNAi therapeutics" encompasses both siRNAs and miRNAs, aligning with current pharmacological criteria and supporting the development of broader RNAi therapies. This unified approach facilitates clearer communication among researchers, clinicians, and educators, ensuring accurate and comprehensive naming of therapeutic agents.