RGLS4326 preferentially distributes to kidney tubules and cysts. RGLS4326 (a single 30?mg/kg SC injection) is rapidly absorbed into plasma, showing Tmax of ≤1?h, Cmax of 8.5?μg/mL, and half-life of <4?h in wild-type mice[1].
In vivo administration of RGLS4326 also upregulates the expression of the direct miR-17 target genes Pkd1 and Pkd2[1].
| Animal Model: | Pkd2-KO mice[1] |
| Dosage: | 20?mg/kg |
| Administration: | SC injection |
| Result: | Compared to non-cystic control kidneys, polycystic kidneys of PBS-treated Pkd2-KO mice exhibit an age-dependent progressive decline in miR-17 PD-Sig, indicative of increasing miR-17 activity with disease progression.
Administration of RGLS4326 reversed this decline in miR-17 PD-Sig, indicating a sustained functional inhibition of miR-17. |
