Figure 5.
In vitro gymnotic delivery and silencing correlates with in vivo gene silencing. (A) Increased potency of an anti-ApoB 3′,5′-end-capped LNA–phosphorothioate 12-mer gap-mer (SPC3716) versus a 16-mer (SPC3302) after 6 days of in vitro gymnotic delivery to Huh-7 cells. ApoB mRNA silencing data are presented as the average ± SD (n = 3; *P < 0.0001 by Student’s t-test assuming unequal variances). (B) In vivo silencing of intra-hepatic ApoB mRNA expression in female NMRI mice after intravenous delivery (5 mg/kg i.v., Days 0, 1 and 2), demonstrating the increase in potency for the 12-mer versus the 16-mer. Data are presented as the average ± SD (n = 3; **P < 0.02 by Student’s t-test assuming unequal variances). (C) In vitro lipofection (Lipofectamine 2000) of the 12-mer and 16-mer anti-ApoB oligomers into Huh-7 human hepatoma cells, demonstrating the increased potency of the latter compared with its 12-mer counterpart. In contrast to the in vitro gymnotic delivery data, these results are inversely correlated with the in vivo data. Data are presented as the average ± SD (n = 3).