Increased metabolic stability should improve biological efficiency and could in part explain the higher efficacy of (R-Ahx-R) 4 -PMO as compared to (Arg) n -PMO and Tat 48-60 -PMO, as discussed previously (3) . However, the (R-Ahx-R) 4 portion of (R-Ahx-R) 4 -PMO was found to be degraded in intact cells (11) . We therefore synthesized (r-Ahx-R) 4 -PMO (compound 13 in Figure 3A ) in which one of the two L-Arg residues in each R-Ahx-R repeat was replaced by a D-Arg (r) residue. Unexpectedly, (r-Ahx-R) 4 -PMO was significantly less efficient in splicing correction than (R-Ahx-R) 4 -PMO ( Figure 3B ). Both L-and D-Arg-containing peptides have similar hydrophobicities ( Figure 3C ). Interestingly, (r-Ahx-R) 4 -PMO has a signficantly higher affinity for heparan sulfate than the parent (R-Ahx-R) 4 -PMO ( Figure 3D ), thus pointing again to the role played by this parameter in splicing correction efficiency.