Surprisingly, the replacement of L-arginine with D-arginine enhanced neither uptake nor antisense activity for oligoarginine, or X-and B-containing conjugates. In the case of (RX) 8 ÀPMO, the replacement actually caused a small but statistically significant decrease in activity. Our observation is different from the results reported by others (20, 21) who found that D-CPPs had higher cellular uptake than L-CPPs, although no biological functional cargo was used in their study. The difference between results may be due to the type and size of cargos and the cell lines used for the assays. Whether the use of D-arginine-containing peptides results in superior CPPÀPMO functional activity in vivo remains to be tested.