Design of nucleic acid binding molecules with non-watson crick and non-canonical pairing based on artificial mutation consensus sequences to counter escape mutations
AssigneeCity of Hope
InventorsJohn J. ROSSI, Ulrike JUNG
Life of this patent
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Abstract
Universal nucleic acid binding molecules (e.g., antisense oligonucleotides or RNAi molecules) having an inhibitory or activating nucleic acid sequence which binds a receiving nucleic acid sequence (e.g., RNA or DNA) are provided. In some embodiments, the universal nucleic acid binding molecules bind the receiving nucleic acid sequence (e.g., RNA or DNA) via at least one non-Watson Crick or non-canonical paired base.
Claims18
-9. (canceled)
A method of treating a subject infected with a target virus, comprising administering a therapeutically effective amount of a universal nucleic acid binding molecule which comprises an inhibitory or activating nucleic acid sequence that binds a receiving nucleic acid sequence via at least one Watson Crick, one non-Watson Crick or one non-canonical pairing;
- wherein the universal nucleic acid binding molecule activates or suppresses the expression or activity of a target molecule.
(canceled)
(canceled)
A method of designing a universal nucleic acid binding molecule comprising
- generating an inhibitory or activating nucleic acid sequence by
- (i) generating a consensus sequence derived from two or more receiving nucleic acid sequences of host or foreign origin and converting the consensus sequence into an International Union of Pure and Applied Chemistry (IUPAC) sequence code by randomly or selectively replacing U or G's with a corresponding ambiguous IUPAC coded base (Y or R);
- or
- (ii) generating an artificial target sequence from one target nucleic acid sequence of host of foreign origin by randomly or selectively replacing U or G's with a corresponding ambiguous IUPAC coded base (Y or R);
- substituting each corresponding ambiguous base with a base that allows for Watson-Crick, non-Watson-Crick, and non-canonical pairings;
- and
- selecting one or more inhibitory RNA molecules using an RNAi selection method, an antisense oligonucleotide selection protocol, or an RNA-based transcriptional activation or inhibition selection method.
Dependencies are inferred from the claim text.