Liposomes containing oligonucleotides

Abstract

It is possible to radiosensitize tumor cells by administration of compositions containing the Human antisense c-raf-1 oligodeoxyribonucleotide (ODN/oligo) sequence: 5'-GTGCTCCATTGATGC-3' (SEQ. ID. NO: 1) wherein only the end bases are phosphorothioated is a preferred embodiment. Antisense sequences of up to 40 bases which contain this sequence, such as 5'-CCTGTATGTGCTCCATTGATGCAGC-3' (SEQ ID NO: 2) may be used in accord with the teachings of this disclosure. Compositions comprising a cationic liposome of dimethyldioctadecyl ammonium bromide, phosphatidylcholine and cholesterol may be used as a carrier system. The liposomes provide a new carrier system that is particularly useful for administration of sequences for therapy.

1 . A composition comprising a cationic liposome comprising a cationic liposome containing a cationic lipid, phosphatidylcholine, cholesterol and an antisense oligonucleotide comprising a raf antisense oligonucleotide wherein the antisense oligonucleotide comprises a sequence of the formula 5′-CCTGTATGTGCTCCATTGATGCAGC-3′ (SEQ ID NO: 2) and wherein only the terminal bases of said oligonucleotide are phosphorothioated.  
     
     
         2 . (canceled)  
     
     
         3 . (canceled)  
     
     
         4 . (canceled)  
     
     
         5 . The composition of  claim 1  further comprising a pharmaceutically acceptable carrier.  
     
     
         6 . (canceled)  
     
     
         7 . The composition of  claim 5 , wherein the pharmaceutically acceptable carrier is isotonic.  
     
     
         8 . The composition of  claim 7 , wherein the pharmaceutically acceptable carrier is a buffered isotonic solution.  
     
     
         9 . A method of radiosensitizing tumor tissue by administration of a radiosensitizing effective amount of least one antisense oligonucleotide of no more than 40 bases comprising the sequence 5′-CCTGTATGTGCTCCATTGATGCAGC-3′ (SEQ ID NO: 2), wherein the radiosensitizing effective amount comprises a dosage that delivers a serum concentration of about 1 μg/mL to 1000 μg/mL.  
     
     
         10 . The method of  claim 9 , wherein the oligonucleotide is phosphorothioated at only the end nucleotides.  
     
     
         11 . (canceled)  
     
     
         12 . The method of  claim 9 , wherein the oligonucleotide is administered intravenously.  
     
     
         13 . The method of  claim 9 , wherein the oligonucleotide is administered directly to the target tissue.  
     
     
         14 . The method of  claim 9 , wherein the oligonucleotide is administered into the arterial supply to the target tissue.  
     
     
         15 . (canceled)  
     
     
         16 . (canceled)  
     
     
         17 . (canceled)