Figure 4.

Metabolic stabilization of the 5΄ phosphate increases retention in both primary and secondary tissues. (A) Bar graphs showing the concentrations of 5΄-hydroxyl (5΄-OH), 5΄-phosphate (5΄-P), or and 5΄-(E)-vinylphosphonate (5΄-VP) hsiRNA guide strands and their metabolites in liver (primary tissue), kidneys, heart and spleen (secondary tissues), one week after intravenous (IV) or subcutaneous (SC) injection. Concentrations measured by PNA hybridization assay. Bar graphs show the mean ± SD, n = 5 mice per group. (B) Summary of fold change in concentrations of 5΄-P and 5΄-VP hsiRNA guide strands compared to 5΄-OH hsiRNA guide strand. Fold changes are color-coded: high fold changes in red and low fold changes in white. Fold changed were calculated by dividing average hsiRNA concentrations in respective organs from n = 5 mice per group.