RNA interference (RNAi) is a mechanism of controlling gene activity used in most eukaryotic cells. Small interfering RNAs (siRNA) are double stranded RNA (dsRNA) molecules that trigger direct homology-dependent control of gene activity. The small dsRNA molecules are recognized by RNAi enzymatic machinery which leads to degradation of target mRNA. In mammalian cells siRNA are produced from cleavage of longer dsRNA precursors by the RNase II endonuclease Dicer. siRNA molecules can also be synthesized by chemical or biological methods.
Micro RNA (miRNA) are another arm of RNAi. miRNA are single stranded molecules that regulate expression of multiple mRNAs while siRNA molecules inhibit one specific target mRNA. The single-stranded miRNA guide the miRISC complex to target mRNAs and result in gene silencing by translational repression, degradation or cleavage. Whereas siRNA must be completely complementary to target mRNA miRNA can be partially complementary to its target RNA.
- Givosiran (Givlaari) from Alynlam Pharmaceuticals is a treatment for acute hepatic porphyria, a rare genetic condition that leads to the buildup of toxic polypyrin molecules (FDA approved)
- Leqvio (inclisiran) from Novartis , an siRNA drug for treatment of hypercholesterolemia or mixed dyslipidemia (European Commission approval)
- Lumasiran (Oxlumo) from Alnylam Pharmaceuticals is a treatment for the rare genetic disorder known as primary hyperoxaluria type 1 (FDA approved, EMA approved)
- Patisiran (Onpattro) from Alnylam is an RNAi treatment for a rare genetic disorder known as hereditary transthyretin amyloidosis that causes buildup of the protein transthyretin in the nervous system (FDA approved)
