On the other hand, the inclusion of nonnatural amino acids as aminohexanoic acid in (R-Ahx-R) 4 was expected to increase the metabolic stability of these conjugates and as a consequence to increase their biological efficiency. This assumption has to be tempered since the (R-Ahx-R) repeats are linked by arg-arg peptide bonds which are amenable to proteolysis by trypsin-like enzymes. Indeed recent studies in our group indicated that (R-Ahx-R) 4 -PMO conjugates were rapidly degraded in cells at these arg-arg bonds (11) . We have therefore investigated a (r-Ahx-R) 4 -PMO conjugate (with r standing for D-Arg) in terms of cell uptake and splicing correction activity.