| abstract |
The use of compounds for the delivery of nucleic acids, as well as conjugates of these compounds with nucleic acids, in particular siRNAs, are provided. Stabilized siRNAs that are useful when covalently binding to the compound and are co-administered with a delivery polymer to achieve mRNA suppression in vivo are also described. In particular, the invention provides the use of a compound of the formula (I) for the delivery of nucleic acids, wherein: Y is a linker group selected from - (CH2) 3 OC (O) -N- (CH2CH2-O ) p-CH2CH2 R1 is -C 1-6 alkyl; - (CH2) -naphthyl; or - (CH2) m-phenyl, phenyl that is unsubstituted or up to four times substituted with a substituent independently selected from: -NO2, -CN, Halogen, -O- (CH2) -phenyl, -O- (C1-6 ) alkyl, or -C (O) -NH2 R2 is hydrogen; - (CH2) k-N-C (Ph) 3, phenyl rings that are unsubstituted or independently substituted with -O- (C1-4) alkyl; - (CH2) k-C (O) -NH2 - (CH2) k-phenyl; - (C1-6) alkyl, which is unsubstituted or substituted once with -S-CH3 R3 is -NH-phenyl, a phenyl group which is further substituted with a substituent independently selected from - (CH2) -OH; or - (CH2) -O-C (O) O- (4-nitro-phenyl); k is 1, 2, 3, 4, 5, 6; m is 1, 2, 3 or 4; n is 0 or 1; and p is an integer of the 20. |