FIGURE 6.

Interplay of hybridization rate and stability on antisense activity. (A) Predicted mRNA dynamics as a function of hybridization rate for (A) unstable (δ_m = 0.03 min⁻¹), (B) moderately stable (δ_m = 0.003 min⁻¹), and (C) very stable (δ_m = 0.0003 min⁻¹) oligonucleotides. In each case (A–C), the hybridization rate constants are k_a = {0.1, 1.0, and 10.0} μM⁻¹ min⁻¹. (D) Experimentally observed dynamics, measured using real-time polymerase chain reaction of the rat gp130 mRNA in H35 cells treated with PS (moderate stability) oligonucleotides selected for fast binding and slow binding, respectively.