Figure 5.

(A) Comparing the effect of introducing 2′-OMe, MOP, R-5′-methyl and R-5′-ethyl DNA modifications on potency and hepatotoxicity of ASOs targeting HDAC2, FXI and Dynamin 2 mRNA (Average ALT = 27 ± 5 IU/l for the PBS group). (B–F) Dose response curves for reducing the target mRNA in the liver in mice. Mice (Balb/c, n = 3/group) were injected subcutaneously with ASO (150, 50, 16.7, 5.6 and 1.9 mg/kg) and euthanized after 72 h. Livers were harvested and reduction in the levels of target mRNAs was measured using qRT-PCR. Plasma ALT values were measured on a clinical analyzer at study termination. Data indicated with asterix were collected from a different experiment using the same study design as indicated above. Blue letters indicate constrained Ethyl (cEt), black indicate DNA and red indicate 5′-alkyl DNA nucleotides. All ASOs were fully phosphorothioate (PS) modified.