Patent ID: 8575123

Claim:
A modular composition, comprising a nucleic acid, at least one endosomolytic component, and at least one targeting ligand, the composition having the formula: wherein is the nucleic acid; E is the endosomolytic component; L is the targeting ligand; x represents independently for each occurrence 0 or 1; y represents independently for each occurrence 1,2,3,4,5, or 6; z in formula (I) is 1,2,3,4,5, or 6 in one instance, and 0,1,2,3,4,5, or 6 in the other instance; and z in formula (II) represents independently for each occurrence 1,2,3,4,5, or 6; A is a linking moiety selected from the group consisting of: wherein Z 1 represents independently for each occurrence O or S; Z 2 represents independently for each occurrence —OH, —OM, -Oalkyl, -Oaryl, -Oaralkyl, —SH, —SM, -Salkyl, -Saryl, -aralkyl, —N(R 3 )R 4 , —C(R 11 ) 2 ) m N(R 11 ) 2 , —N(R 11 )(C(R 11 ) 2 ) m N(R 11 ) 2 , or alkyl; R 3 and R 4 represent independently H or alkyl; or R 3 and R 4 taken together form a 3-, 4-, 5-, 6-, or 7-membered ring; R 11 represents independently for each occurrence hydrogen or alkyl; M represents independently for each occurrence an alkali metal or a transition metal with an overall charge of +1; R 8 represents independently for each occurrence hydrogen, alkyl, aryl, aralkyl, acyl, silyl, a bond to the nucleic acid, or, when combined with B 10 , a bond between linking moieties; B 10 is a bond between A and the nucleic acid or, when combined with R 8 , is a bond between linking moieties; A′ is a direct bond or a tether having the formula: —[(P-Q-R) q —X—(P′-Q′-R′) q′ ] q″ -T-, wherein: P, R, T, P′ and R′ are each independently absent, CO, NH, O, S, OC(O), NHC(O), CH 2 , CH 2 NH, CH 2 O; NHCH(R a )C(O), —C(O)—CH(R a )—NH—, C(O)—(optionally substituted alkyl)-NH—, CH═N—O, cyclyl, heterocyclyl, aryl or heteroaryl; R 50 and R 51 are independently alkyl, substitituted alkyl, or R 50 and R 51 taken together form a cyclic ring; Q and Q′ are each independently for each occurrence absent, —(CH 2 ) n —, —C(R 40 )(R 41 )(CH 2 ) n —, —(CH 2 ) n C(R 40 )(R 41 )—, —(CH 2 CH 2 O) m CH 2 CH 2 —, —(CH 2 CH 2 O) m CH 2 CH 2 NH—, aryl, heteroaryl, cyclyl, or heterocyclyl; X is absent or a cleavable linking group; R a is H or an amino acid side chain; R 40 and R 41 are each independently H, CH 3 , OH, SH or N(R x ) 2 ; R x is, for each occurrence, H, methyl, ethyl, propyl, isopropyl, butyl or benzyl; q, q′ and q″ are each independently 0-30; n is, for each occurrence, an integer from 1-20; and m is, for each occurrence, an integer from 0-50; provided that E and L are each present at least once.