siRNA potency enhancement via chemical modifications of nucleotide bases at the 5′-end of the siRNA guide strand

Knockdown activity of ApoB-targeting siRNAs in mouse liver at 48 h (A) and 168 h (B) with adenine, 6-mCEPh-purine, or 6-PBuS-purine at the 5′-end of the guide strand. (C) IC₅₀ values (mpk) obtained when mice were treated with 5′ modified siRNAs, determined after 48 h (A) and 168 h (B) of administration. (D) Total cholesterol in mouse plasma after the administration of various concentrations of LNP/siRNA. Data are represented as the means ± SD, n = 3. P = 0.001 (a): Two-way ANOVA, (b): One-way ANOVA, (*) P < 0.05, (**) P < 0.01: unpaired t-test_Bonferroni correction.