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Kafe 바로가기국가/구분 | United States(US) Patent 등록 |
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국제특허분류(IPC7판) |
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출원번호 | US-0569939 (2004-03-03) |
등록번호 | US-8394947 (2013-03-12) |
국제출원번호 | PCT/US2004/017485 (2004-03-03) |
§371/§102 date | 20071203 (20071203) |
국제공개번호 | WO2005/120230 (2005-12-22) |
발명자 / 주소 |
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출원인 / 주소 |
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대리인 / 주소 |
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인용정보 | 피인용 횟수 : 0 인용 특허 : 397 |
The present invention provides oligomeric compounds having sufficient complementarity to hybridize to a nucleic acid target and methods for their use in modulating gene expression. In one embodiment the oligomeric compounds comprise double stranded constructs wherein one of the strands capable of hy
The present invention provides oligomeric compounds having sufficient complementarity to hybridize to a nucleic acid target and methods for their use in modulating gene expression. In one embodiment the oligomeric compounds comprise double stranded constructs wherein one of the strands capable of hybridizing to a nucleic acid target, and has a plurality of modified ribofuranosyl nucleosides at defined locations. The presence of modifications at such defined positions greatly enhances the properties of the corresponding compositions.
1. A composition comprising a first oligomeric compound and a second oligomeric compound, wherein: the first oligomeric compound is capable of hybridizing with at least a portion of the second oligomeric compound and to a selected target nucleic acid;each of the first and the second oligomeric compo
1. A composition comprising a first oligomeric compound and a second oligomeric compound, wherein: the first oligomeric compound is capable of hybridizing with at least a portion of the second oligomeric compound and to a selected target nucleic acid;each of the first and the second oligomeric compounds independently comprises a contiguous sequence of from about 19 to about 23 nucleosides linked by internucleoside linking groups;each of the first and the second oligomeric compounds optionally comprises a phosphate group, a 3′ or 5′-overhang or a conjugate group; andthe first oligomeric compound having a plurality of modified ribofuranosyl nucleosides at defined positions, and the modified ribofuranosyl nucleosides consisting of 2′-OCH3 modified nucleosides at positions 6, 7, 10, 11, 17, 18 and 19 of the first oligomeric compound counting from the terminal 5′-hybridizing nucleoside. 2. The composition of claim 1 wherein the first and the second oligomeric compounds are independently from about 19 to about 21 nucleosides in length. 3. The composition of claim 1 wherein the first and the second oligomeric compounds are each independently 19 or 20 nucleosides in length. 4. The composition of claim 1 wherein the second oligomeric compound comprises unmodified β-D-ribofuranosyl nucleosides. 5. The composition of claim 1 wherein the nucleosides of each of the first and the second oligomeric compounds are linked by phosphodiester internucleoside linking groups. 6. The composition of claim 1 wherein the nucleosides of each of the first and the second oligomeric compounds are linked by phosphorothioate internucleoside linking groups. 7. The composition of claim 1 wherein the nucleosides of each of the first and the second oligomeric compounds are independently linked by phosphorothioate or phosphodiester internucleoside linking groups. 8. The composition of claim 1 wherein the second oligomeric compound comprises modified nucleosides. 9. The composition of claim 1 wherein the second oligomeric compound comprises modified ribofuranosyl nucleosides alternating with unmodified β-D-ribofuranosyl nucleosides. 10. The composition of claim 9 wherein the modified ribofuranosyl nucleosides are either 2′-OCH3 modified nucleosides or 2′-methoxyethoxy modified nucleosides. 11. The composition of claim 1 wherein the terminal 5′-hybridizing nucleoside and the terminal 3′-hybridizing nucleoside of the second oligomeric compound are unmodified β-D-ribofuranosyl nucleosides, and the nucleosides in between the terminal hybridizing nucleosides are 2′-OCH3 modified nucleosides. 12. The composition of claim 1 wherein the terminal 5′-hybridizing nucleoside of the second oligomeric compound is an unmodified β-D-ribofuranosyl nucleoside, the nucleosides between the terminal 5′-hybridizing nucleoside and the terminal 3′-hybridizing nucleoside are 2′-OCH3 modified nucleosides, and the terminal 3′-hybridizing nucleoside is a 2′-OCH3 modified nucleoside. 13. The composition of claim 1 wherein the second oligomeric compound comprises one or more modified ribofuranosyl nucleosides independently selected from 2′-fluoro ribofuranosyl sugar moieties, 4′-thio ribofuranosyl moieties, 2′-OCH3 ribofuranosyl sugar moieties, 2′-methoxyethoxy ribofuranosyl moieties, modified ribofuranosyl moieties having a 4′-CH2—O-2′-bridge, and ribofuranosyl moieties having a 4′-(CH2)2—O-2′-bridge. 14. The composition of claim 1, wherein the second oligomeric compound comprises one or more modified ribofuranosyl nucleosides independently selected from 2′-fluoro ribofuranosyl sugar moieties and 2′-methoxyethoxy ribofuranosyl moieties. 15. The composition of claim 1 additionally comprising one or more moieties or conjugates for enhancing the activity, cellular distribution or cellular uptake of the resulting oligomeric compounds.
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