Patent ID: 6235887
Filing Date: 2001-05-22
Classification: C07H,C12Q

Abstract:
A method making an oligonucleotide, comprising the steps:(a) selecting a first oligonucleotide comprising a first covalent modification and a second covalent modification, said first covalent modification selected from the group consisting of a modified sugar, a modified base and a modified linkage and said second covalent modification selected from the group consisting of a modified sugar, a modified base and a modified linkage, wherein said first covalent modification increases the binding affinity of said first oligonucleotide for a complementary nucleic acid sequence relative to an otherwise identical unmodified second oligonucleotide that does not comprise said first covalent modification or said second covalent modification, and wherein said second covalent modification decreases the binding affinity of said first oligonucleotide for the complementary nucleic acid sequence relative to said otherwise identical unmodified second oligonucleotide that does not comprise the first covalent modification or the second covalent modification and wherein said second covalent modification results in a property selected from the group consisting of increased nuclease stability and enhanced cellular permeation in said first oligonucleotide for a complementary nucleic acid sequence relative to said otherwise identical unmodified second oligonucleotide;(b) measuring the affinity of said first oligonucleotide for a complementary nucleic acid sequence;(c) selecting an oligonucleotide of step (b) having a binding affinity for the complementary nucleic acid sequence that is greater than the sum of the increased binding affinity and the decreased binding affinity; and(d) preparing the oligonucleotide of step (c).