Table 2.
List of siRNAs reported in the text, their mechanism of action, and potential uses, and benefits.
| siRNA | Mechanism of Action | Potential Uses and Benefits |
|---|---|---|
| Inclisiran | PCSK9 mRNA degradation in the liver and inhibition of PCSK9 synthesis and secretion, leading to increased LDLR expression on the surface of hepatocytes and reduced circulating LDL-C levels | Significant, sustained and safe LDL-C lowering in patients at high and very high CV risk that do not reach their LDL-C goal with traditional lipid-lowering therapy (statins and ezetimibe) and/or are statin-intolerant. Potential reduction in the risk of MACE in patients at high and very high CV risk. Optimal adherence to therapy, with only two injections in a year |
| Olpasiran and Lepodisiran | LPA mRNA degradation in the liver and inhibition of Lp(a) assembly and secretion | Significant, sustained, and safe Lp(a) lowering in patients with high Lp(a) circulating levels. Potential reduction in the risk of ischemic CV disease, ASCVD, and calcific valvular aortic stenosis. Reduction in OxPL-apoB levels, a biomarker strongly associated with ASCVD. Optimal adherence to therapy, with only two or three injections in a year |
| ARO-APOC3 | APOC3 mRNA degradation in the liver and inhibition of APOC3 synthesis and secretion, leading to increased triglycerides clearance and hepatocyte uptake of triglyceride-rich lipoproteins | Significant, sustained, and safe triglycerides lowering in patients with hypertriglyceridemia and chylomicronemia. Potential reduction in the risk of ASCVD and pancreatitis in patients with hypertriglyceridemia and chylomicronemia |
| Patisiran and Vutrisiran | TTR mRNA degradation in the liver and inhibition of TTR synthesis and secretion, thereby preventing its abnormal accumulation in amyloidosis | Significant, sustained, and safe TTR lowering in patients with ATTR amyloidosis. Improvement of neurological symptoms and quality of life in patients with ATTR-polyneuropathy. Improvement of cardiac parameters and symptoms in patients with ATTR-cardiomyopathy. Increase in survival in patients with ATTR amyloidosis. Potential reduction in all-cause mortality and CV events in patients with ATTR-cardiomyopathy. Optimal adherence to therapy, with only four injections in a year (only for vutrisiran) |
| Zilebesiran | AGT mRNA degradation in the liver and inhibition of AGT synthesis and secretion, thereby preventing the production of angiotensin peptides and inhibiting the renin-angiotensin-aldosterone system | Significant, sustained, and safe systolic and diastolic BP lowering in patients with uncontrolled hypertension. Reduction in the risk of CV events in patients with uncontrolled or resistant hypertension. Optimal adherence to therapy, with only two or four injections in a year |
PCSK9: proprotein convertase subtilisin/kexin type 9; LDLR: low-density lipoprotein receptor; CV: cardiovascular; LDL-C: low-density lipoprotein cholesterol; MACE: major adverse cardiovascular events; LPA: apolipoprotein(a) gene; Lp(a): lipoprotein(a); ASCVD: atherosclerotic cardiovascular disease; APOC3: apolipoprotein C-III; ATTR: transthyretin amyloidosis; AGT: angiotensinogen; BP: blood pressure.