RGLS4326

RGLS4326 is a first-in-class, short antisense oligonucleotide inhibitor of microRNA-17 (miR-17), developed as a potential disease-modifying therapy for autosomal dominant polycystic kidney disease (ADPKD). It is a chemically modified, single-stranded oligonucleotide designed to bind with full complementarity to the miR-17 seed sequence. By inhibiting miR-17 function in kidney collecting duct cells and displacing it from translationally active polysomes, RGLS4326 de-represses multiple miR-17 mRNA targets including PKD1 and PKD2. This leads to upregulation of these genes and suppression of cyst growth in preclinical models. The drug preferentially distributes to the kidney after subcutaneous administration and demonstrates favorable pharmacokinetic properties with rapid absorption and renal excretion. Clinical development has focused on ADPKD[1][2][5][6].