Most (R-X-R) 4 -PMO conjugates were synthesized as fluorescent FAM conjugates to allow assessment of celular uptake by FACS analysis and by fluorescence microscopy. As seen in Figure 4 , there is no correlation between cellular uptake and splicing correction activity. Increasing the spacing between arginine residues (compounds 1-7) leads to decreased cellular uptake in parallel to heparin affinity but on the contrary leads to increased splicing correction. Remarkably, (R-Ahx-R) 4 -PMO which was the most active conjugate in this series in terms of splicing correction turned out the less efficient in terms of cellular uptake. In addition, changing the hydrophobicity of the spacer (compounds 8-11) or modifying the stereochemistry of Arg (compounds 5 and 13) had no significant impact on cellular uptake.