Positionally modified siRNA constructs
First Claim
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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; and
the 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.
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Abstract
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.
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Citations
15 Claims
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1. A composition comprising a first oligomeric compound and a second oligomeric compound, wherein:
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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. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
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Specification