Polycationic sterol derivatives as transfection agents

Abstract

A compound capable of acting as a cationic lipid is described. The compound comprises a cholesterol group having linked thereto a head group; wherein the head group is more positive than the head group of DC-Chol.

1 . A compound capable of acting as a cationic lipid, the compound comprising a cholesterol group having linked thereto a head group; and wherein the head group is more positive than the head group of DC-Chol; but wherein the compound is not synthesised by reacting spermidine and cholesterol chloroformate in CH 2 Cl 2  in the presence of N,N-diisoprophylethylamine.  
     
     
         2 . A compound according to  claim 1  wherein the cholesterol group is cholesterol.  
     
     
         3 . A compound according to  claim 1  or  claim 2  wherein the cholesterol group is linked to the head group via a carbamoyl linkage.  
     
     
         4 . A compound according to any one of  claims 1  to  3  wherein the head group is a polyamine group.  
     
     
         5 . A compound according to  claim 4  wherein the polyamine group is a naturally occurring polyamine.  
     
     
         6 . A compound according to  claim 5  wherein the polyamine is any one of spermidine, spermine or caldopentamine.  
     
     
         7 . A compound according to any one of  claims 1  to  6  in admixture with or associated with a nucleotide sequence.  
     
     
         8 . A process of preparing a compound according to any one of  claims 1  to  7  comprising reacting a cholesterol group with a head group.  
     
     
         9 . A process according to  claim 8  wherein the process comprises at least one step utilising aza-Wittig methodology.  
     
     
         10 . A compound according to any one of  claims 1  to  7  or a compound when prepared by the process of  claim 8  or  claim 9  for use in therapy.  
     
     
         11 . Use of a compound according to any one of  claims 1  to  7  or a compound when prepared by the process of  claim 8  or  claim 9  in the manufacture of a medicament for the treatment of genetic disorder or condition or disease.  
     
     
         12 . A cationic liposome formed from the compound according to any one of  claims 1  to  7  or a compound when prepared by the process of  claim 8  or  claim 9 .  
     
     
         13 . A method of preparing a cationic liposome comprising forming the cationic liposome from the compound according to any one of  claims 1  to  7  or a compound when prepared by the process of  claim 8  or  claim 9 .  
     
     
         14 . A cationic liposome according to  claim 12  or a cationic liposome as prepared by the method of  claim 13  for use in therapy.  
     
     
         15 . Use of a cationic liposome according to  claim 12  or a cationic liposome as prepared by the method of  claim 13  in the manufacture of a medicament for the treatment of genetic disorder or condition or disease.  
     
     
         16 . A combination of a nucleotide sequence and any one or more of: a compound according to any one of  claims 1  to  7 , a compound when prepared by the process of  claim 8  or  claim 9 , a cationic liposome according to  claim 12 , or a cationic liposome as prepared by the method of  claim 13 .  
     
     
         17 . A combination according to  claim 16  for use in therapy.  
     
     
         18 . Use of a combination according to  claim 17  in the manufacture of a medicament for the treatment of genetic disorder or condition or disease.  
     
     
         19 . A pharmaceutical composition comprising a compound according to any one of  claims 1  to  7  or a compound when prepared by the process of  claim 8  or  claim 9  admixed with a pharmaceutical and, optionally, admixed with a pharmaceutically acceptable diluent, carrier or excipient.  
     
     
         20 . A pharmaceutical composition comprising a cationic liposome according to  claim 12  or a cationic liposome as prepared by the method of  claim 13  admixed with a pharmaceutical and, optionally, admixed with a pharmaceutically acceptable diluent, carrier or excipient.  
     
     
         21 . A compound or a cationic liposome substantially as described herein and with reference to any one of the Figures.  
     
     
         22 . A process substantially as described herein and with reference to any one of the Figures.