Antagomir

Antagomirs are synthetic, chemically modified oligonucleotides designed to silence endogenous microRNA (miRNA) activity in vivo. They function primarily through sequence-specific binding to their target miRNA, leading to miRNA inactivation and subsequent upregulation of the genes targeted by the miRNA.

Antagomirs are typically cholesterol-conjugated to enhance their bioavailability and tissue uptake, particularly by the liver. The cholesterol modification facilitates entry into cells via endocytosis. Other chemical modifications, such as 2'-O-methylation or locked nucleic acids (LNAs), improve their stability and resistance to degradation by nucleases in the bloodstream.

The mechanism of action involves binding to the miRNA, sterically hindering it from interacting with its mRNA targets. This prevents the miRNA from repressing the translation or promoting the degradation of the target mRNA, thereby increasing protein expression.

Antagomirs are used extensively in biological research to investigate the roles of specific miRNAs in various physiological and pathological processes. By inhibiting a miRNA's function, researchers can study the downstream effects on gene expression, cellular pathways, and disease development. Areas of research include cancer, cardiovascular disease, metabolic disorders, and inflammatory diseases.

Antagomirs are generally delivered systemically, typically via intravenous or subcutaneous injection. Their efficacy and duration of action can vary depending on the specific antagomir sequence, chemical modifications, dosage, and the target tissue.