Optimized in vivo delivery system with endosomolytic agents for nucleic acid conjugates

A conjugated hairpin nucleic acid molecule which has the following formula:

• wherein N is a nucleotide, n is an integer from 15 to 195, the underlined N refers to a nucleotide having or not a modified phosphodiester backbone, L′ is a linker selected from the group consisting of an abasic nucleotide, a polyether, a polyamine, a polyamide, a peptide, a carbohydrate, a lipid, a polyhydrocarbon, an oligoethylene glycol, hexaethyleneglycol, tetradeoxythymidylate (T4), 1,19-bis(phospho)-8-hydraza-2-hydroxy-4-oxa-9-oxo-nonadecane and 2,19-bis(phosphor)-8-hydraza-1-hydroxy-4-oxa-9-oxo-nonadecane;
• m is 1 and L is a linker, C is a molecule facilitating endocytosis selected from the group consisting of single or double chain fatty acids, tocopherol, folates or folic acid, cholesterol, sugar, peptide and protein, and wherein C is conjugated via L to the linker L′.