The number of X residues affects both the nuclear antisense activity and the toxicity of conjugates. The CPPÀPMO conjugate with 8 X residues [(RX) 8 ÀPMO] had the highest activity followed by one with 5 Xs [(RXR) 4 ÀPMO] (Figures 1 and 4) . However, these conjugates were toxic to cells at higher concentrations, which may be a concern when considering potential applications for in vivo delivery of PMO. Replacement of all 8 Xs with Bs decreased both toxicity and antisense activity. The combination of 3-4 Xs with several B residues yielded CPPs with no detectable toxicity, and at some concentrations several of them had similar antisense activity as (RX) 8 ÀPMO. We think this type of CPP, having Bs and fewer than 5 Xs, will offer balanced activity and low toxicity as well as the stability, and have considerable potential for delivery of therapeutic AOs. Further investigation into the toxicity and activity versus dosing levels of these CPPs in vivo is warranted.