Lipids, lipid complexes and use thereof

Abstract

The present invention is related to a compound according to formula (I), wherein R 1 and R 2 are each and independently selected from the group comprising alkyl; n is any integer between 1 and 4; R 3 is an acyl selected from the group comprising lysyl, ornithyl, 2,4-diaminobutyryl, histidyl and an acyl moiety according to formula (II), wherein m is any integer from 1 to 3 and Y − is a pharmaceutically acceptable anion.

1 . A siRNA molecule comprising a double stranded siRNA molecule selected from: 
       
         
           
                 
                 
               
                     
                 
                   siRNA name 
                   Sequence 5′ to 3′ 
                 
                     
                 
                     
                 
                 
                 
                 
               
                   CD31-1 s 
                   ccaacuucaccauccagaa 
                   (SEQ ID NO: 13) 
                 
                   CD31-1 as 
                   uucuggauggugaaguugg; 
                   (SEQ ID NO: 14) 
                 
                     
                 
                   CD31-2 s 
                   ggugauagccccgguggau 
                   (SEQ ID NO: 15) 
                 
                   CD31-2 as 
                   auccaccggggcuaucacc; 
                   (SEQ ID NO: 16) 
                 
                     
                 
                   CD31-6 s 
                   ccacuucugaacuccaaca 
                   (SEQ ID NO: 17) 
                 
                   CD31-6 as 
                   uguuggaguucagaagugg; 
                   (SEQ ID NO: 18)  
                 
                 
               
                   or 
                 
                     
                 
                 
                 
                 
               
                   CD31-8 s 
                   cagauacucuagaacggaa 
                   (SEQ ID NO: 19) 
                 
                   CD31-8 as 
                   uuccguucuagaguaucug. 
                   (SEQ ID NO: 20) 
                 
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
               
            
             
                
                
               
            
             
                
                
                
               
            
           
         
       
     
     
         2 . The siRNA molecule according to  claim 1 , wherein said siRNA molecule is a double stranded siRNA molecule that is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 nucleotides in length. 
     
     
         3 . The siRNA molecule according to  claim 2 , wherein said siRNA molecule is a double stranded siRNA molecule that is 23 nucleotides in length. 
     
     
         4 . The siRNA molecule according to  claim 2 , wherein said siRNA molecule is a double stranded siRNA molecule that is 25 nucleotides in length. 
     
     
         5 . The siRNA molecule according to  claim 2 , wherein the 3′ end of said siRNA molecule has an overhang. 
     
     
         6 . The siRNA molecule according to  claim 2 , wherein said siRNA molecule has alternating 2′-O-methyl sugar modifications on both strands, wherein unmodified nucleotides face modified on the opposite strand. 
     
     
         7 . The siRNA molecule according to  claim 2 , wherein said siRNA molecule is chemically modified. 
     
     
         8 . The siRNA molecule according to  claim 1 , wherein said siRNA molecule is 
       
         
           
                 
                 
                 
               
                   CD31-8 s 
                   cagauacucuagaacggaa 
                   (SEQ ID NO: 19) 
                 
                   CD31-8 as 
                   uuccguucuagaguaucug. 
                   (SEQ ID NO: 20) 
                 
             
                
                
               
            
           
         
       
     
     
         9 . A siRNA molecule comprising a siRNA molecule selected from: 
       
         
           
                 
                 
                 
               
                   CD31-1 s 
                   c c a a c u u c a c c a u c c a g a a 
                   (SEQ ID NO: 13) 
                 
                   CD31-1 as 
                     u u c u g g a u g g u g a a g u u g g ; 
                   (SEQ ID NO: 14) 
                 
                     
                 
                   CD31-2 s 
                   g g u g a u a g c c c c g g u g g a u 
                   (SEQ ID NO: 15) 
                 
                   CD31-2 as 
                     a u c c a c c g g g g c u a u c a c c ; 
                   (SEQ ID NO: 16) 
                 
                     
                 
                   CD31-6 s 
                   c c a c u u c u g a a c u c c a a c a 
                   (SEQ ID NO: 17) 
                 
                   CD31-6 as  
                     u g u u g g a g u u c a g a a g u g g ; 
                   (SEQ ID NO: 18) 
                 
                 
               
                   or 
                 
                     
                 
                 
                 
                 
               
                   CD31-8 s 
                   c a g a u a c u c u a g a a c g g a a 
                   (SEQ ID NO: 19) 
                 
                   CD31-8 as 
                     u u c c g u u c u a g a g u a u c u g   
                   (SEQ ID NO: 20) 
                 
             
                
                
                
                
                
                
                
                
               
            
             
                
                
               
            
             
                
                
               
            
           
         
       
       and wherein underlined nucleotides in said siRNA molecule have alternating 2′-O-methyl sugar modifications. 
     
     
         10 . The siRNA molecule according to  claim 9 , wherein said siRNA molecule is a double stranded siRNA molecule that is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 nucleotides in length. 
     
     
         11 . The siRNA molecule according to  claim 10 , wherein said siRNA molecule is a double stranded siRNA molecule that is 23 nucleotides in length. 
     
     
         12 . The siRNA molecule according to  claim 10 , wherein said siRNA molecule is a double stranded siRNA molecule that is 25 nucleotides in length. 
     
     
         13 . The siRNA molecule according to  claim 10 , wherein the 3′ end of said siRNA molecule has an overhang. 
     
     
         14 . The siRNA molecule according to  claim 9 , wherein said siRNA molecule is 
       
         
           
                 
                 
                 
               
                   CD31-8 s 
                   c a g a u a c u c u a g a a c g g a a 
                   (SEQ ID NO: 19) 
                 
                   CD31-8 as 
                     u u c c g u u c u a g a g u a u c u g . 
                   (SEQ ID NO: 20) 
                 
             
                
                
               
            
           
         
       
     
     
         15 . A composition comprising a siRNA molecule according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         16 . A composition comprising a siRNA molecule according to  claim 9  and a pharmaceutically acceptable carrier. 
     
     
         17 . A method of reducing the expression of CD31 in a cell comprising contacting said cell with a composition comprising a siRNA molecule according to  claim 1 . 
     
     
         18 . The method according to  claim 17 , wherein said cell is a vascular endothelial cell, platelet, monocyte, neutrophil or T-cell. 
     
     
         19 . A method of reducing the expression of CD31 in a cell comprising contacting said cell with a composition comprising a siRNA molecule according to  claim 9 . 
     
     
         20 . The method according to  claim 19 , wherein said cell is a vascular endothelial cell, platelet, monocyte, neutrophil or T-cell.