Patent ID: 8426377

Claim:
An iRNA agent comprising a first strand and optionally a second strand, wherein at least one subunit having a formula (I) is incorporated into at least one of the strands: 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 T-R d , in which T is a tether having the formula -(E′) s -Δ-(E″) t ; and R d H or a ligand, wherein: each of E′ and E″ is a linking group; Δ is a hydrocarbon chain that optionally includes one or more linking groups, G; each of s and t is, independently, 0 or 1; and at least one of the E′, E″ or G linking groups is a cleavable disulfide (—SS—) group; provided that one of s or t is 1, or Δ includes at least one G; 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 H or 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; and n is 1-4; provided that X is N(CO)R 7 or NR 7 ; or one of R 5 , R 6 , R 11 , and R 12 is C(O)NHR 7 ; or R 14 is present.