Ligand-conjugated monomers

1. A conjugate comprising an oligonucleotide agent and a ligand represented by R d , wherein at least one subunit having a formula (I) is incorporated into said oligonucleotide agent:

wherein:

X is N(CO)R 7 , NR 7 or CH 2 ;

Y is NR 8 , O, S, CR 9 R 10 , or absent;

Z is CR 11 R 12 or absent;

Each of R 1 , R 2 , R 3 , R 4 , R 9 , and R 10 is, independently, H, OR a , OR b , (CH 2 ) n OR a , or (CH 2 ) n OR b , provided that at least one of R 1 , R 2 , R 3 , R 4 , R 9 , and R 10 is OR a or OR b and that at least one of R 1 , R 2 , R 3 , R 4 , R 9 , and R 10 is (CH 2 ) n OR a , or (CH 2 ) n OR b ;

Each of R 5 , R 6 , R 11 , and R 12 is, independently, H, C 1 -C 6 alkyl optionally substituted with 1-3 R 13 , or C(O)NHR 7 ; or R 5 and R 11 together are C 3 -C 8 cycloalkyl optionally substituted with R 14 ;

R 7 is R d ; or C 1 -C 20 alkyl substituted with NR c R d or NHC(O)R d ;

R 8 is C 1 -C 6 alkyl;

R 13 is hydroxy, C 1 -C 4 alkoxy, or halo;

R 14 is NR c R 7 ;

R a is: H or

R b is:

Each of A and C is, independently, O or S;

B is OH, O − , or

R c is H or C 1 -C 6 alkyl;

R d is a carbohydrate radical or a steroid radical optionally tethered to at least one carbohydrate radical; and

n is 1-4,

wherein the oligonucleotide agent can target a substantially complementary miRNA.

2. The conjugate of claim 1 , wherein X is N(CO)R 7 or NR 7 , Y is CR 9 R 10 , and Z is absent.

3. The conjugate of claim 2 , wherein R 7 is (CH 2 ) 5 NHR d or (CH 2 ) 5 NHC(O)R d .

4. The conjugate of claim 3 , wherein R d is a steroid radical optionally tethered to at least one carbohydrate radical.

5. The conjugate of claim 4 , wherein R d is a cholesterol radical.

6. The conjugate of claim 2 , wherein R 1 is (CH 2 ) n R b and R 9 is OR a .

7. The conjugate of claim 6 , wherein R 1 and R 9 are trans.

8. The conjugate of claim 6 , wherein n is 1.

9. The conjugate of claim 2 , wherein R 1 is (CH 2 ) n R b and R 9 is OR b .

10. The conjugate of claim 2 , wherein R 1 is (CH 2 ) n OR a and R 9 is OR b .

11. The conjugate of claim 2 , wherein R 3 is (CH 2 ) n OR b and R 9 is OR a .

12. The conjugate of claim 2 , wherein R 3 is (CH 2 ) n OR b and R 9 is OR b .

13. The conjugate of claim 2 , wherein R 3 is (CH 2 ) n OR a and R 9 is OR b .

14. The conjugate of claim 2 , wherein R 3 is OR a and R 9 is (CH 2 ) n OR b .

15. The conjugate of claim 2 , wherein R 3 is OR b and R 9 is (CH 2 ) n OR b .

16. The conjugate of claim 2 , wherein R 3 is OR b and R 9 is (CH 2 ) n OR a .

17. The conjugate of claim 1 , wherein X is N(CO)R 7 or NR 7 , Y is CR 9 R 10 , Z is CR 11 R 12 .

18. The conjugate of claim 1 , wherein X is N(CO)R 7 or NR 7 , Y is NR 8 , and Z is CR 11 R 12 .

19. The conjugate of claim 1 , wherein X is N(CO)R 7 or NR 7 , Y is O, and Z is CR 11 R 12 .

20. The conjugate of claim 1 , wherein X is CH 2 ; Y is CR 9 R 10 ; Z is CR 11 R 12 , and R 5 and R 11 together form C 6 cycloalkyl.

21. The conjugate of claim 1 , wherein X is CH 2 ; Y is CR 9 R 10 ; Z is CR 11 R 12 , and R 5 and R 11 together form C 5 cycloalkyl.

22. The conjugate of claim 1 , wherein the ligand represented by R d is attached to a 3′ terminal subunit.

23. The conjugate of claim 1 , wherein the ligand represented by R d is attached to a 5′ terminal subunit.

24. The conjugate of claim 1 , wherein the ligand represented by R d is attached to an internal subunit.

25. The conjugate of claim 1 , wherein the miRNA is selected from the group consisting of miR-21, miR-16, miR-22, miR-122, miR-155, miR-192, miR-194, and miR-375.

26. A pharmaceutical composition comprising a conjugate of claim 1 and a pharmaceutically acceptable carrier.

27. A kit comprising a conjugate of claim 1 , a sterile container in which the conjugate is enclosed, and instructions for use.

28. The conjugate of claim 1 , wherein R d is a carbohydrate radical.