Whether too much affinity for heparan sulfates could be detrimental for dissociation of the heparan-bound material in endocytic vesicles and for endosomal escape is a possibilty but it is unfortunately not amenable to direct demonstration. It is worth pointing out that similar conclusions could be drawn from our previous comparison of (Arg) 9 -PMO, Tat-PMO and (R-Ahx-R) 4 -PMO conjugates. (R-Ahx-R) 4 -PMO was found more active in the splicing correction assay despite binding less efficiently to heparin and being taken up less well than the parent (Arg) 9 -PMO and than Tat-PMO (3).