Antisense oligonucleotide (metabolic)

Class

Antisense oligonucleotide therapeutic

This entry describes a class of therapeutics known as RNA-targeted oligonucleotides—antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs)—applied to genes that drive metabolic disease. Rather than blocking a protein after it is made, these molecules intervene earlier, at the messenger RNA (mRNA) stage, preventing a disease-associated protein from being produced in the first place. This is useful when a condition results from too much of a normal protein, such as a lipid-carrying particle that raises cardiovascular risk, or from a mutant protein that is toxic regardless of quantity. Because many metabolic regulators are produced predominantly in the liver, these agents are often engineered for selective uptake by liver cells, allowing effective gene silencing at low, infrequent doses. The rationale for this modality over conventional small molecules or antibodies is that it acts upstream, at the genetic information level, and can address targets—such as certain structural or scaffold proteins—that lack a druggable pocket for a conventional inhibitor. This class is broadly relevant to dyslipidemias, hypertriglyceridemia, and other inherited or acquired disorders of lipid and protein metabolism, where reducing the production of a specific circulating protein can lower disease risk or slow progression.