In vitro GalNAc and linker metabolism for siRNA8 in cultured hepatocytes
| Analyte | Total AUC siRNA8 Sense Strand Metabolite Profile | ||
|---|---|---|---|
| Rat | Monkey | Human | |
| % | |||
| −3 GalNAc | Not detected | 48.7 | 45.0 |
| −3 GalNAc, −1linker1 | Not detected | 20.3 | 27.5 |
| −3 GalNAc, −1linker1, −1linker2 | Not detected | 5.2 | Not detected |
| −3 GalNAc, −2linker1 | Not detected | 12.2 | 14.9 |
| −3 GalNAc, −2linker1, −1linker2 | Not detected | 3.6 | Not detected |
| −3 GalNAc, −3linker1, | 99.5 | 8.5 | 11.0 |
| −3 GalNAc, −3linker1, −1linker2 | Not detected | 1.6 | Not detected |
| Full-length siRNA8 | 66.6 | 71.0 | 74.9 |
| AS(N-1)3′ siRNA8 | 29.7 | 21.2 | 15.9 |