Small interfering RNA (siRNA)-based therapeutics

In early studies in simple organisms and mammalian cell lines, small interfering RNA (siRNA) molecules were found to allow experimental cleavage of intracellular messenger RNA (mRNA; the transcription product of a cell gene), reducing the levels of the proteins that would otherwise be formed by the action of the mRNA, thereby 'silencing' a specific gene. Researchers subsequently assessed the effects of this class of molecule in patients with various genetic conditions (eg, hereditary amyloidosis) that could benefit from reductions in the excessive quantities of harmful proteins (eg, amyloid). Due to the hydrophilic (non-fat-soluble) nature of the molecules, they have been formulated as lipid nanoparticles to aid transport into cells or conjugated to molecules with an ability to target certain cells in the body (eg, hepatocytes) to aid specificity of action. Their intracellular effects may last up to several months before they are broken down and inactivated. As they need to be composed of an exact complementary sequence to be able to cleave the target mRNA, they are thought to have few unwanted effects apart from infusion or injection site reactions. Several siRNA medicines have been licensed and many other products are in development for genetic hepatic, cardiovascular and ocular conditions.