| 摘要 |
The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a lipophilic moiety. e.g., cholesterol, is directly, or indirectly, tethered. The invention also relates to methods of making and using such modified iRNA agents. |
| 主权项 |
1. An iRNA agent comprising a first strand and a second strand, wherein at least two subunits having a formula (I) are incorporated into at least one of said strands:wherein:
X is N(CO)R7, NR7 or CH2; Y is NR8, O, S, CR9R10, or absent; Z is CR11R12 or absent; each of R1, R2, R3, R4, R9, and R10 is, independently, H, ORa, ORb, (CH2)nORa, or (CH2)nORb, provided that at least one of R1, R2, R3, R4, R9, and R10 is ORa or ORb and that at least one of R1, R2, R3, R4, R9, and R10 is (CH2)nORa, or (CH2)nORb; each of R5, R6, R11, and R12 is, independently, H, C1-C6 alkyl optionally substituted with 1-3 R13, or C(O)NHR7; or R5 and R11 together are C3-C8 cycloalkyl optionally substituted with R14; R7 is Rd; or C1-C20 alkyl substituted with NRcRd or NHC(O)Rd; R8 is C1-C6 alkyl; R13 is hydroxy, C1-C4 alkoxy, or halo; R14 is NRcR7; Ra is H or Rb is H orwherein the Strand in each occurrence is independently the first strand or second strand of the iRNA agent;
each of A and C is, independently, O or S; and B is OH, O−, or Rc is H or C1-C6 alkyl; Rd is H or a ligand; and n is 1-4. |
