Fig. 1

Discovery of RGLS4326, a chemically modified oligonucleotide inhibitor of miR-17. a Screening cascade used for the discovery of RGLS4326. b Over 190 anti-miR-17 oligonucleotides of diverse chemical designs were screened at 10 μM in a miR-17 HeLa cell luciferase assay and plotted in ascending order of potency (n = 1/oligonucleotides). Selected oligonucleotides including RGLS4326 (green) are highlighted for illustration purposes. c A subset of oligonucleotides was tested in WT/C57BL6 mice for their ability to engage and displace miR-17 in the kidney 7 days after a single 30 mg kg⁻¹ SC dose (n = 4). d A smaller set of oligonucleotides were further tested in the JCK/C57BL6 PKD model for miR-17 target engagement (n = 5). e–f Preferential distribution to kidney over liver 7 days after a single 30 mg kg⁻¹ SC dose of selected oligonucleotides in WT/C57BL6 (n = 4) and JCK/C57BL6 mice (n = 5) are shown. g Chemical modifications, base sequence, and corresponding complementarity to the miR-17 family of mature miRNAs for RGLS4326 is illustrated. Error bars represent standard error of means. Source data for Fig. 1b–f is provided in Source data files