Oligonucleotide analogues
AssigneeExiqon A/S
InventorsJesper Wengel, Poul Nielsen
Life of this patent
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Abstract
The present invention relates to novel bicyclic and tricyclic nucleoside and nucleotide analogues as well as to oligonucleotides comprising such elements. The nucleotide analogues, LNAs (Locked Nucleoside Analogues), are able to provide valuable improvements to oligonucleotides with respect to affinity and specificity towards complementary RNA and DNA oligomers. The novel type of LNA modified oligonucleotides, as well as the LNAs as such, are useful in a wide range of diagnostic applications as well as therapeutic applications. Among these can be mentioned antisense applications, PCR applications, strand displacement oligomers, as substrates for nucleic acid polymerases, as nucleotide based drugs, etc. The present invention also relates to such applications.
Claims42
A method for using an oligomer to isolate, purify, amplify, detect, identify, quantify or capture a natural or synthetic nucleic acid, the oligomer being modified with at least one Locked Nucleic Acid (LNA), the method comprising the step of contacting LNA-modified oligomer with the nucleic acid under conditions sufficient to form a binding complex to isolate, purify, amplify, detect, identify, quantify or capture the nucleic acid, wherein the LNA is represented by the following general formula I:
- wherein X is selected from —O—;
- B is selected from hydrogen, hydroxy, optionally substituted C1-4-alkoxy, optionally substituted C1-4-alkyl, optionally substituted C1-4-acyloxy, nucleobases, DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups, and ligands;
- P designates a radical position for an internucleoside linkage to a succeeding monomer or a 5′-terminal group, optionally including the substituent R5,
- one of the substituents R2, R2*, R3, and R3* is a group P* which designates an internucleoside linkage or a 3′-terminal group;
- the substituents R4* and R2*, together designating the biradical —(CR*R*)r—O—(CR*R*)s—, each R* is independently selected from hydrogen, halogen, hydroxy, mercapto, amino, optionally substituted C1-6-alkoxy, optionally substituted C1-6-alkyl, DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups, and ligands, and r is 0 (zero) and s is 1, or r is 1 and s is 0 (zero);
- and
- each of the substituents R1*, R2, R3, R5, and R5*, which are present and not involved in P or P* is independently selected from hydrogen, optionally substituted C1-12-alkyl, optionally substituted C2-12-alkenyl, optionally substituted C2-12-alkynyl, hydroxy, C1-12-alkoxy, C2-12-alkenyloxy, carboxy, C1-12-alkoxycarbonyl, C1-12-alkylcarbonyl, formyl, aryl, aryloxy, carbonyl, aryloxy, arylcarbonyl, heteroaryl, heteroaryloxy-carbonyl, heteroaryloxy, heteroarylcarbonyl, amino, mono- and di(C1-6-alkyl)amino, carbamoyl, mono- and di(C1-6-alkyl)-amino-carbonyl, amino-C1-6-alkyl-aminocarbonyl, mono- and di(C1-6-alkyl)amino-C1-6-alkyl-aminocarbonyl, C1-6-alkyl-carbonylamino, carbamido, C1-6-alkanoyloxy, sulphono, C1-6-alkylsulphonyloxy, nitro, azido, sulphanyl, C1-6-alkylthio, halogen, DNA intercalators, photochemically active groups, thermochemically active groups, chelating groups, reporter groups, and ligands, where aryl and heteroaryl may be optionally substituted,
- and basic salts and acid addition salts thereof, wherein a natural or synthetic nucleic acid is isolated, purified, amplified, detected, identified, quantified, or captured using the oligomer.
Dependencies are inferred from the claim text.