Oligoarginine, RX, RXR and RB panels. The CPP conjugates with the highest nuclear antisense activities were (RXR) 4 À and (RX) 8 ÀPMO. Figure 3A and B show luciferase activity normalized to protein of cells treated with various conjugates at 1 and 5 mM for 24 h. At both concentrations, (RX) 8 À and (RXR) 4 ÀPMO were more effective than the other conjugates tested, with the difference more prominent in serum-containing medium at 1 mM than at 5 mM. Cells treated with 1 mM of either conjugate had luciferase activity 10-15-fold over the background while the remaining conjugates yielded about a 2-4-fold over the background (Figure 3A ). At 5 mM, all conjugates generated higher luciferase activity Figure 2 . Cellular uptake of the CPPÀPMOF conjugates. pLuc705 cells were treated with carboxyfluorescein-tagged PMOs conjugated to CPPs in OptiMEM with or without 10% serum for 24 h, followed by flow cytometry analysis. Data are presented as mean fluorescence (MF) AE SD of six data points from two independent experiments. (A) Cells treated with 2 mM of R 8 2, R 9 2, (RXR) 4 2, (RX) 8 2 or (RB) 8 2PMOF conjugates. (B) Cells treated with 2 mM of (RX) 8 2, (RX) 7 2, (RX) 5 2, (RB) 8 2, (RB) 7 2 or (RB) 5 2PMOF conjugates in the absence of serum. (C) Cells treated with 2 mM of (RXR) 4 2 or R 9 2PMOF in media containing 0, 10, 30 or 60% serum. (D) Cells treated with (RX) 8 2 or (rX) 8 2PMOF in media containing 10% serum. than at 1 mM, with (RX) 8 ÀPMO and (RXR) 4 ÀPMO again the most effective, followed by (RB) 8 ÀPMO ( Figure 3B ). Figure 3C shows that at 10 mM, the activity of RX or RB conjugates decreased as the number of RX or RB repeats in the CPP decreased. The peptides with 5 or 3 RX or RB repeats, (RX) 5 , (RX) 3 (RB) 5 or (RB) 3 , generated much lower luciferase activity than those with 8 and 7 repeats.