Fig. 4: An AR CAG TNR based HP with longer CAG repeats more effectively kills cells through RNAi.

A Location of the CAG repeat region in the AR gene. The mean length of the CAG repeat in the AR gene in different SBMA patient populations ranges between 44 and 48. The maximum repeat length is around 68, whereas the normal length is between 9 and 34 [3, 17, 75]. B Structure of the HP mimetics used. ΔG value (in kcal/mol) is given. C, D, left panel, change in confluency over time of NB7, HeLa parental or HeLa AGO2 k.o. cells transfected with 2.5 nM (for NB7 cells) or 10 nM (for HeLa cells) of different HPs. D, right panel, viability of indicated cells 4 days after transfection with different HPs (10 nM). Fold change is shown relative to (CAG)21 control. E, left panel, change in confluency over time of 293T parental or AGO2 k.o. cells transfected with 25 nM of either (CAG)21 or 3–17. E, right panel, F, viability of indicated cells 3 days (E) or 4 days (F) after transfection with 25 nM (E) or 10 nM (F) of either (CAG)21 or 3–17. Fold change is shown relative to lipid control. p = values (Student’s t-test) are shown (D, right panel, E, right panel, F). Average of 3-6 replicates are shown −/+SE (C, D, left panel, E, left panel) and mean of 3–6 replicates are shown −/+SD (D, right panel, E).