ISIS-217376

ISIS-217376 is an antisense oligonucleotide (ASO) designed to specifically inhibit the expression of acyl-coenzyme A:diacylglycerol acyltransferase 2 (DGAT2). Developed by Ionis Pharmaceuticals (formerly ISIS Pharmaceuticals), this 20-base chimeric oligonucleotide features 2′-O-(2-methoxy)-ethyl (2′-MOE) modifications on the first and last five bases to enhance stability and target affinity. By binding to DGAT2 mRNA, ISIS-217376 facilitates its degradation, thereby reducing the synthesis of triglycerides in the liver and adipose tissue. Preclinical studies in obese mouse models have shown that treatment with ISIS-217376 significantly improves hepatic steatosis and attenuates hyperlipidemia by inhibiting hepatic lipogenesis and increasing fatty acid oxidation, without the adverse effects on skin permeability or survival observed in DGAT2-null mice.