Modeling hybridization kinetics

Formation of complementary base pairs between nucleic acids over a short region (less than or equal to 15 nucleotides) is described by a kinetic model in which the intermediate state is assumed to be locally single stranded. The model enables calculation of a rate factor that is proportional to the rate constant for hybridization under steady-state reaction conditions. Rate factors calculated for various sites in acetylcholinesterase mRNA correlated with sites found previously to be experimentally accessible for hybridization to antisense oligo-nucleotides. Hybridization rate of longer antisense oligodeoxynucleotides was modeled by calculation of a maximal rate factor for all possible 15-nucleotide segments of a given antisense molecule. Maximal rate factor calculated for a set of antisense oligonucleotides correlated (r = 0.95) with initial rate of hybridization reported previously. Two other models proposed for identifying accessible sites for hybridization were less predictive than the rate factor calculation. (C) 2003 Elsevier Science Inc. All rights reserved.