Design, delivery and efficacy testing of therapeutic nucleic acids used to inhibit hepatitis C virus gene expression in vitro and in vivo

Figure 1 HCV 5’-non-coding region. The pseudonot region and stem loop IV including the start AUG are indicated in bold font as optimum target sequences for ODN binding.

Figure 2 Plasmid constructs to analyze inhibition of HCV translation in vitro (upper) and in vivo (lower). Expression is directed either by the T7-promoter or the CMV immediate early promoter.

Figure 3 Modified hammerhead RZ and HCV target sequence. The G_16.2,C_16.1, A₁₇ recognition site (nts. 346-348), in which cleavage occurs, is marked by an arrow. All nucleotides are 2’-O-ally l-ribonucleotides except G₅, A₆, G₈ and G₁₂ (light gray), which are unmodified ribonucleotides. The position of the A to l exchange (medium gray) and the start AUG of the HCV template are indicated.

Figure 4 Schematic representation of a taurocholic acid-coupled antisense oligodeoxynucleotide. R: oligodeoxynucleotide 5’-end.