Oligomeric compounds comprising tricyclic nucleosides and methods for their use
AssigneeIonis Pharmaceuticals, Inc.
InventorsEric E. Swayze, Andrew M. Siwkowski, Punit P. Seth, Thazha P. Prakash
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Abstract
The present disclosure provides tricyclic nucleosides, oligomeric compounds comprising at least one of the tricyclic nucleosides and methods of using the oligomeric compounds. The methods provided herein include contacting a cell or administering to an animal at least one of the oligomeric compounds. In certain embodiments, the oligomeric compounds hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
Claims18
An oligomeric compound comprising at least one tricyclic nucleoside having formula II:
- wherein independently for each of said tricyclic nucleosides having formula II:
- Bx is a heterocyclic base moiety;
- one of T1 and T2 is an internucleoside linking group attaching said tricyclic nucleoside of formula II to said oligomeric compound and the other of T1 and T2 is hydroxyl, a protected hydroxyl, a 5′ or 3′-terminal group selected from one or more conjugate groups, capping groups and phosphate moieties or an internucleoside linking group attaching said tricyclic nucleoside of formula II to said oligomeric compound;
- q1, q2, q3 and q4 are each H;
- z1 is H and z2 is F;
- and
- wherein said oligomeric compound comprises from about 8 to about 40 linked monomeric subunits and is complementary to at least a portion of a target RNA.
A tricyclic nucleoside having formula III:
- wherein:
- Bx is a heterocyclic base moiety;
- one of T3 and T4 is H or a hydroxyl protecting group and the other of T3 and T4 is H, a hydroxyl protecting group or a reactive phosphorus group;
- q1, q2, q3 and q4 are each H;
- and
- z1 is H and z2 is F.
Dependencies are inferred from the claim text.