DOUBLE STRAND COMPOSITIONS COMPRISING DIFFERENTIALLY MODIFIED STRANDS FOR USE IN GENE MODULATION
First Claim
1. A composition comprising first and second chemically synthesized oligomeric compounds wherein:
- at least a portion of the first oligomeric compound is complementary to and capable of hybridizing to a selected nucleic acid target;
a portion of from about 12 to about 24 nucleosides of the first oligomeric compound is complementary to the second oligomeric compound;
one of the first and second oligomeric compounds is an asymmetric gapped oligomeric compound;
the other of the first and the second oligomeric compounds comprises nucleosides linked by internucleoside linking groups wherein the sequence of linked nucleosides defines an alternating motif having the formula;
5′
-A(-L-B-L-A)n(-L-B)nn-3′
wherein;
each L is, independently, an internucleoside linking group;
one of each A or each B is a β
-D-ribonucleoside;
the other of each A or each B is a sugar modified nucleoside wherein each sugar modified nucleoside is identical;
n is from about 7 to about 11;
nn is 0or 1;
the composition optionally further comprises one or more overhangs, phosphate moieties, conjugate groups or capping groups.
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Abstract
The present invention provides double stranded compositions wherein each strand is modified to have a motif defined by positioning of β-D-ribonucleosides and sugar modified nucleosides. More particularly, the present compositions comprise one strand having a gapped motif and another strand having a gapped motif, a hemimer motif, a blockmer motif, a fully modified motif, a positionally modified motif or an alternating motif. At least one of the strands has complementarity to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In some embodiments, the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.
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Citations
44 Claims
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1. A composition comprising first and second chemically synthesized oligomeric compounds wherein:
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at least a portion of the first oligomeric compound is complementary to and capable of hybridizing to a selected nucleic acid target;
a portion of from about 12 to about 24 nucleosides of the first oligomeric compound is complementary to the second oligomeric compound;
one of the first and second oligomeric compounds is an asymmetric gapped oligomeric compound;
the other of the first and the second oligomeric compounds comprises nucleosides linked by internucleoside linking groups wherein the sequence of linked nucleosides defines an alternating motif having the formula;
5′
-A(-L-B-L-A)n(-L-B)nn-3′wherein;
each L is, independently, an internucleoside linking group;
one of each A or each B is a β
-D-ribonucleoside;
the other of each A or each B is a sugar modified nucleoside wherein each sugar modified nucleoside is identical;
n is from about 7 to about 11;
nn is 0or 1;
the composition optionally further comprises one or more overhangs, phosphate moieties, conjugate groups or capping groups. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44)
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Specification