Small interfering RNA: Potential applications for nephrologists
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61
Small interfering RNA (siRNAs) are double-stranded RNAs of around 20 base pairs in length that trigger RNAi machinery, which promotes degradation of a target mRNA avoiding protein translation. SiRNAs are liver-targeted, using tris-N-acetylgalactosamine (GalNAc) as the targeting ligand. This discovery was awarded the Nobel Prize in Physiology or Medicine in 2006 and has led to substantial therapeutic advances. The field of application is broad, and development of these siRNA has been very rapid. In 2018, patisiran was approved to treat hereditary transthyretin amyloidosis. This first drug approval demonstrated the security and efficacy of such a product. Since then, drugs have been developed for acute hepatic porphyria and primary hyperoxaluria. The current pipeline for new siRNA development is ambitious, and clinical trials are ongoing in nephrology, including in IgA nephropathy. Very common diseases such as hypertension or hypercholesterolemia are also being explored.© 2022 Published by Elsevier Masson SAS on behalf of the Société francophone de néphrologie, dialyse et transplantation.
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