Altogether, it is clear that CPP-steric block ON conjugates need to be active at lower doses for systemic administration and clinical applications. It is hoped that a better understanding of the structural determinants required for cell binding, cellular uptake and endosome escape will be helpful for the rational design of more potent and/or less cytotoxic CPPs. The manuscript essentially aims at comparing series of (R-Ahx-R) 4 -PMO conjugates analogs differing in Arg spacer length, in hydrophobicity of the spacer and in stereochemistry of Arg. Criteria for the comparative evaluation of these conjugates include cellular uptake, splicing correction efficiency, affinity for heparin, hydrophobicity and synthetic membrane-destabilizing potential.