Chemically modified oligonucleotides
AssigneeAlnylam Pharmaceuticals, Inc.
InventorsMuthiah Manoharan, Venkitasamy Kesavan, Kallanthottathil G. Rajeev
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Abstract
This invention relates composition and methods for making and using chemically modified oligonucleotides agents for inhibiting gene expression.
Claims23
An isolated oligonucleotide agent, comprising a nucleotide sequence consisting of from 12 to 23 nucleotides in length sufficiently complementary to a microRNA target sequence of about 12 to 23 nucleotides, wherein the nucleotide sequence of the oligonucleotide agent differs by no more than 1 or 2 nucleotides from full complementary to the microRNA target sequence and wherein said oligonucleotide agent has the structure (I)
- (5′) QxQz1(Qy)nQz2Qz3Qz4Q-L (3′) (I)
- wherein
- Q is a 2′-O-methyl modified nucleoside;
- x, z1, z2, z3, and z4 are all
- One of A and B is S while the other is O;
- n=6-17;
- L is
- wherein:
- X is N(CO)R7, or NR7;
- each of R1, R3 and R9, is, independently, H, OH, or —CH2ORb provided that at least one of R1, R3, or R9 is OH and at least one of R1, R3 or R9 is —CH2ORb;
- R7 is C1-C20 alkyl substituted with NRcRd or NHC(O)Rd;
- Rc is H or C1-C6 alkyl;
- Rd is a carbohydrate radical;
- or a steroid radical, which is optionally tethered to at least one carbohydrate radical;
- and
- Rb is
- one of E and F is S while the other is O.
Dependencies are inferred from the claim text.