Résumé
PNAs conjugated to the cell penetrating peptide (CPP) R-6-Penetratin (R6Pen) are useful reagents for sequence-specific targeting of RNAs within cells in the absence of an added transfection agent. We show that a variant of R6Pen-KPNA705K(3) conjugate, where the basic domain and GG linker at the C-terminus of the peptide part is replaced by (R-AhX)(4), maintains good activity in a HeLa pLuc705 splice correction assay, which is a test of nuclear delivery. Replacement of the N-terminal R-6 section by (R-Ahx-R)(3) improved the activity. We also describe a new CPP H2F2R9F2, which has a similar level of activity to R6Pen when disulfide conjugated to KPNA705K. These conjugates appear to enter cells by an energy-dependent endocytotic pathway. R6Pen-KPNAK(3) targeted to miR-122 blocks miR-122 activity in human liver cells in the absence of a transfection agent. KPNAK(3) that lacks a CPP also has this blocking ability, showing that a CPP is not necessary for targeting a microRNA in the cytosol of liver cells. Such PNAs may find utility in therapeutic applications.