Serum effect on activity. The effect of serum on the antisense activity of the conjugates depended on the CPP sequences, as shown in Figure 3A -D. Addition of 10% serum to the medium decreased the activity of oligoarginineÀPMO conjugates (R 8 ÀPMO and R 9 ÀPMO) but increased activity of conjugates containing RXR, RX and RB repeats. The addition of 10% serum nearly doubled the luciferase activity of (RXR) 4 À, (RX) 8 À and (RB) 8 ÀPMO at 5 mM ( Figure 3B ). We further studied this effect for (RXR) 4 ÀPMO up to 60% serum. While the activity almost doubled as the serum concentration increased from 0 to 10%, it gradually decreased as the serum concentration increased to 60%, at which activity was similar to that in 0% serum which was still significantly above the background. This 'up and down' profile was also observed with the 1 mM (RXR) 4 ÀPMO treatment. Unlike (RXR) 4 ÀPMO, the luciferase activity of R 8 ÀPMO or R 9 ÀPMO (data not shown) only decreased as the serum concentration increased, with an approximately 30% reduction in 10% serum and no activity in 60% serum. R 8 ÀPMO or R 9 ÀPMO did not display any detectable activity at 1 mM, regardless of the serum concentration (data not shown).