New arginine-rich CPPs have recently been proposed for the nuclear delivery of neutral ON analogs as PMO (3) or PNA (10) . They represent a significant improvement over first generation CPPs as Tat, Pen, oligoarginine or oligolysine since they allow a sequence-specific splicing correction at lower concentrations (EC 50 ranging between 0.5 and 2.0 mM) which do not lead to membrane permeabilization and, importantly, do not require endomosomolytic drugs or treatments. Importantly as well, (R-Ahx-R) 4 -PMO conjugates lead to a sustained expression of dystrophin in skeletal muscles when injected intraperitoneally (5 mg/kg) in DMD mice (25, 26) . These encouraging data should however be tempered since these may be still high doses too close to the toxic doses found in other murine models (6) . The present SAR study has therefore been initiated in order to delineate step(s) limiting the splice correcting activity of (R-Ahx-R) 4 -PMO as well as important molecular features of the (R-Ahx-R) 4 -CPP moiety.