Method for selectively ranking sequences for antisense targeting
AssigneeBoard of Regents, The University of Texas
InventorsDonald M. Gray, Chris L. Clark
Life of this patent
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Abstract
A system and method for assessing the minimum number of RNA:DNA sequence combinations whose properties need to be determined for selecting antisense oligonucleotide sequences that will form the most stable hybrid among all those possible in a given target mRNA sequence is provided.
Claims15
A method for selectively ranking nucleic acid molecules comprising antisense oligonucleotide for inhibitory efficiency comprising the steps of:
- determining the fraction of each of a set of 13 nearest-neighbor nucleic acid base pair types in a target sequence zone RNA:ASO-DNA hybrid nucleic acid sequence;
- substituting nearest-neighbor nucleic acid base pair fractions into formulas to determine the fractions of each of a series of 13 nearest-neighbor nucleic acid base pair types to provide determined fractions;
- and
- multiplying the fractions of the 13 nearest-neighbor nucleic acid base pair types by a stability ranking to the nucleic acid antisense sequence;
- wherein the results are ordered to produce a ranking.
A method for selectively ranking nucleic acid molecules comprising an antisense oligonucleotide for inhibitory efficiency comprising the steps of:
- determining the fraction of nearest-neighbor base pair types in each of a set of nucleic acid target sequence zone RNA:ASO-DNA hybrid nucleic acid sequences;
- substituting nearest-neighbor base pairs fractions into formulas to determine the fractions of a series of 13 nearest-neighbor nucleic acid base pair types and ranking said fractions that include the substituted nucleic acid sequences for stability to provide a stability ranking for each of the fractions;
- multiplying the fractions of the 13 nearest-neighbor nucleic acid base pair types by the stability ranking to yield the rank of the antisense oligonucleotide;
- wherein said rank of the antisense oligonucleotide corresponds to the inhibitory efficiency of said antisense oligonucleotide.
A method for selectively ranking an antisense sequence comprising the steps of:
- determining the fraction of nearest-neighbor base triplet types in a set of nucleic acid sequences comprising a target sequence zone DNA:ASO-DNA triplex nucleic acid sequence;
- substituting nearest-neighbor base pairs fractions into formulas to determine the fractions of each of the nearest-neighbor nucleic acid sequence triplet types and ranking said fractions that include the substituted nucleic acid sequence triplet types for stability to provide a stability ranking for each of the nearest-neighbor nucleic acid sequence triplet types;
- and
- multiplying the fractions of the nearest-neighbor triplet types by the stability ranking to yield the rank of the nucleic acid sequence antisense oligonucleotide;
- wherein the results are ordered to produce a ranking.
A method for ranking a nucleic acid antisense sequence for hybridization efficacy comprising the steps of:
- determining the fraction of each type of in a set of nucleic acid sequences comprising a target sequence zone DNA:ASO-DNA triplex sequence;
- substituting nearest-neighbor base pairs fractions into formulas to determine the fractions of each of the 13 nearest-neighbor base nucleic acid sequence triplex types;
- multiplying the fractions of the 13 nearest-neighbor base triplex by the stability ranking to yield the rank of the nucleic acid sequence antisense oligonucleotide;
- and ranking antisense oligonucleotides according to maximum hybridization efficacy.
Dependencies are inferred from the claim text.