UMOD-targeting antisense oligonucleotide

UMOD-targeting antisense oligonucleotides are a class of therapeutic agents designed to selectively or pan-allelically knock down the expression of uromodulin (UMOD). UMOD is nearly exclusively expressed in the epithelial cells of the thick ascending limb of Henle's loop (TAL) in the kidney. Mutations in the UMOD gene lead to autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD), a toxic gain-of-function endoplasmic reticulum (ER) storage disease characterized by the accumulation of misfolded UMOD aggregates, leading to ER stress, tubular cell death, and progressive chronic kidney disease. By targeting UMOD mRNA for degradation or translation blocking, these antisense oligonucleotides aim to reduce the toxic accumulation of UMOD aggregates and alleviate ER stress. Various research groups and companies, including Sarepta Therapeutics and academic institutions like Boston Children's Hospital and the University of Zurich, have investigated UMOD-targeting ASOs (including peptide-conjugated phosphorodiamidate morpholino oligonucleotides, or PPMOs, and gapmer ASOs) in preclinical models.

Other names

UMOD-targeting ASOuromodulin-targeting ASOuromodulin-targeting antisense oligonucleotide