Fig 2: Structures of siRNAs and linkers. Shown from top to bottom are the structures of ß-lactam (blue) functionalized siRNA at the 3' (4) and 5' (5) end targeting human ß-catenin (CTNNB1), the structure of control ß-lactam functionalized siRNA at the 3' end (6) targeting human transthyretin (TTR), and the structure of control siRNA targeting CTNNB1 but lacking the ß-lactam moiety (7). The siRNAs (4–6) were prepared by reaction of the corresponding sense strands (4-6ss) with symmetrical bis-ß-lactam linker (8) followed by annealing with the corresponding antisense strands (4as, 6as). Black circles stand for 2'-OMe and 2'-F-modified nucleosides of the corresponding CTNNB1 and TTR sequences (Supplementary Table S2), orange circles for 2'-O-[2-(methylamino-2-oxoethyl]-5-methyl-uridine containing a 5'-vinylphosphonate (VP) moiety. Yellow bars denote phosphorothioate linkages for exonuclease protection.

Fig 3: CTNNB1 protein knockdown. CTNNB1 protein knockdown in NCI-H929 cells after treatment with 90 nM BCMA (10 and 13) (orange and red, respectively) targeting DVD-ARCs for 7 days at 37°C. Unconjugated anti-BCMA DVD-IgG1s (2) (blue), anti-BCMA DVD-ARC (15) targeting human TTR, and HER2-targeting DVD-ARCs (16 and 17) served as negative controls. Transfected free siRNA (7) served as positive control. The western blot depicted on the top is a representative example from independent triplicates shown as mean ± SEM values on the bottom.