Novel Compositions for the Delivery of Negatively Charged Molecules

Abstract

This invention features permeability enhancer molecules, and methods, to increase membrane permeability of various molecules, such as nucleic acids, polynucleotides, oligonucleotides, enzymatic nucleic acid molecules, antisense nucleic acid molecules, 2-5A antisense chimeras, triplex forming oligonucleotides, decoy RNAs, dsRNAs, siRNAs, aptamers, or antisense nucleic acids containing nucleic acid cleaving chemical groups, peptides, polypeptides, proteins, carbohydrates, steroids, metals and small molecules, thereby facilitating cellular uptake of such molecules.

1 - 10 . (canceled) 
     
     
         11 . A cationic lipid having the formula VIII:
   R 8 -L 2 -Cholesterol   wherein, R 8  is selected from the group consisting of arginyl, N-Boc arginyl, homoarginyl, N-Boc homoarginyl, ornithine, N-Boc ornithine, N-benzyl histidyl, lysyl, N-Boc lysyl, N-methyl arginyl, N-methyl guanidine, guanidine and pyridoxyl: and   L 2  is a linker represented by NH, glycine, N-butyldiamine or guanidine.   
     
     
         12 . The cationic lipid of  claim 11 , wherein said cationic lipid is Boc arginine-cholesterylamide. 
     
     
         13 . The cationic lipid of  claim 11 , wherein said cationic lipid is N-cholesteryl-pyridoxamine. 
     
     
         14 . The cationic lipid of  claim 11 , wherein said cationic lipid is 3′,5′-Di-palmitoyl-2′-deoxy-2′-(N-carboxamidine-beta-alanineamido)uridine. 
     
     
         15 . The cationic lipid of  claim 11 , wherein said cationic lipid is linked to polyethylene glycol (PEG). 
     
     
         16 . The cationic lipid of  claim 15 , wherein said PEG is between about 2000-5000 daltons inclusive.