Nanotubes as Carriers of Nucleic Acids into Cells

Abstract

The present invention is directed to transfection complexes of rosette nanotubes and one or more nucleic acids.

1 . A method of delivering one or more nucleic acids into a cell comprising contacting the cells with a complex of a rosette nanotube and the one or more nucleic acids in a manner to deliver the complex into the cell. 
     
     
         2 . The method of  claim 1  wherein the nanotube is formed from the self-assembly of compounds having the formula 
       
         
           
           
               
               
           
         
         wherein X is CH or nitrogen, R2 is hydrogen or a linker group; Y is absent when R2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R2; and R1 is hydrogen or an aliphatic moiety; and salts thereof. 
       
     
     
         3 . The method of  claim 1  wherein the nanotube is formed from the self-assembly of compounds having the formula 
       
         
           
           
               
               
           
         
         wherein X is CH or nitrogen; R2 is hydrogen or a linker group; Y is absent when R2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R2, and R1 is hydrogen or an aliphatic moiety; and salts thereof. 
       
     
     
         4 . The method of  claim 1  wherein the one or more nucleic acids include DNA, RNA, a gene, a gene fragment, an exon, an intron, intergenic DNA, heterochromatic DNA, messenger RNA, transfer RNA, interference RNA, dsRNA, ssRNA, saRNA, siRNA, miRNA, ribosomal RNA, a ribozyme, eDNA, a recombinant polynucleotide, a branched polynucleotide, a plasmid, a vector, isolated DNA of a sequence, isolated RNA of a sequence, a nucleic acid probe, a molecular beacon or a primer. 
     
     
         5 . The method of  claim 1  wherein the one or more nucleic acids includes siRNA having between about 10 to about 30 nucleic acids in length. 
     
     
         6 . The method of  claim 1  wherein the cell includes an animal, plant or bacterial cells. 
     
     
         7 . A method of treating an individual requiring treatment comprising administering a complex of a rosette nanotube and one or more nucleic acids to the individual in a manner to deliver the one or more nucleic acids into cells within the individual and wherein the cells either express the one or more nucleic acids in a therapeutic manner or the one or more nucleic acids inhibit expression of one or more proteins within the cells in a therapeutic manner. 
     
     
         8 . A method of making a complex comprising mixing together rosette nanotubes and one or more nucleic acids in aqueous media under conditions which cause the rosette nanotubes to combine with the one or more nucleic acids to form a stable complex in aqueous media. 
     
     
         9 . A product made by the process comprising
 mixing together rosette nanotubes and one or more nucleic acids in aqueous media under conditions which cause the rosette nanotubes to combine with the one or more nucleic acids to form a stable complex in aqueous media.   
     
     
         10 . A complex comprising a rosette nanotube including one or more nucleic acids. 
     
     
         11 . A complex comprising one or more nucleic acids and a rosette nanotube formed from the self assembly of compounds having the formula 
       
         
           
           
               
               
           
         
         wherein X is CH or nitrogen; R2 is hydrogen or a linker group; Y is absent when R2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R2; and R1 is hydrogen or an aliphatic moiety; and salts thereof. 
       
     
     
         12 . A transfection complex comprising one or more nucleic acids and a rosette nanotube formed from the self assembly of compounds having the formula 
       
         
           
           
               
               
           
         
         wherein X is CH or nitrogen; R2 is hydrogen or a linker group; Y is absent when R2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R2; and R1 is hydrogen or an aliphatic moiety; and salts thereof. 
       
     
     
         13 . A complex comprising one or more nucleic acids and a rosette nanotube formed from the self assembly in aqueous media of one or more compounds having the formula 
       
         
           
           
               
               
           
         
         wherein X is CH or nitrogen; R2 is hydrogen or a linker group; Y is absent when R2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R2; and R1 is hydrogen or an aliphatic moiety; and salts thereof, 
         and one or more compounds having the formula 
       
       
         
           
           
               
               
           
         
         wherein X is CH or nitrogen; R2 is hydrogen or a linker group; Y is absent when R2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R2; and R1 is hydrogen or an aliphatic moiety; and salts thereof. 
       
     
     
         14 . The method of  claim 2  wherein the aliphatic moiety is a straight chain or a branched alkyl group being saturated or unsaturated. 
     
     
         15 . The method of  claim 3  wherein the aliphatic moiety is a straight chain or a branched alkyl group being saturated or unsaturated. 
     
     
         16 . The complex of  claim 11  wherein the aliphatic moiety is a straight chain or a branched alkyl group being saturated or unsaturated. 
     
     
         17 . The complex of  claim 12  wherein the aliphatic moiety is a straight chain or a branched alkyl group being saturated or unsaturated. 
     
     
         18 . The complex of  claim 13  wherein the aliphatic moiety is a straight chain or a branched alkyl group being saturated or unsaturated. 
     
     
         19 . The method of  claim 2  wherein the linker group is (CH 2 ) n  where n is an integer of 1, 2, 3, or 4, (CH 2 ) 3 CO, 
       
         
           
           
               
               
           
         
       
     
     
         20 . The method of  claim 3  wherein the linker group is (CH 2 ) n  where n is an integer of 1, 2, 3, or 4, (CH 2 ) 3 CO, 
       
         
           
           
               
               
           
         
       
     
     
         21 . The method of  claim 11  wherein the linker group is (CH 2 ) n  where n is an integer of 1, 2, 3, or 4, (CH 2 ) 3 CO, 
       
         
           
           
               
               
           
         
       
     
     
         22 . The method of  claim 12  wherein the linker group is (CH 2 ) n  where n is an integer of 1, 2, 3, or 4, (CH 2 ) 3 CO, 
       
         
           
           
               
               
           
         
       
     
     
         23 . The method of  claim 13  wherein the linker group is (CH 2 ) n  where n is an integer of 1, 2, 3, or 4, (CH 2 ) 3 CO, 
       
         
           
           
               
               
           
         
       
     
     
         24 . A method of making a complex comprising mixing together compounds having the formula 
       
         
           
           
               
               
           
         
         wherein X is CH or nitrogen; R 2  is hydrogen or a linker group; Y is absent when R 2  is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R 2 ; and R 1  is hydrogen or an aliphatic moiety, such as alkyl, straight or branched chain, saturated or unsaturated; and salts thereof. 
         and one or more nucleic acids in aqueous media and sonicating the mixture to cause the compounds to combine with the one or more nucleic acids to form a stable complex in aqueous media. 
       
     
     
         25 . The method of  claim 24  wherein the linker group is (CH 2 ) n , where n is an integer of 1, 2, 3, or 4, (CH 2 ) 3 CO, 
       
         
           
           
               
               
           
         
       
     
     
         26 . The method of  claim 24  wherein the mixture is sonicated and heated to boiling. 
     
     
         27 . A method of making a complex comprising mixing together compounds having the formula 
       
         
           
           
               
               
           
         
         wherein X is CH or nitrogen; R 2  is hydrogen or a linker group; Y is absent when R 2  is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R 2 ; and R 1  is hydrogen or an aliphatic moiety, such as alkyl, straight or branched chain, saturated or unsaturated; and salts thereof 
         and one or more nucleic acids in aqueous media and sonicating the mixture to cause the compounds to combine with the one or more nucleic acids to form a stable complex in aqueous media. 
       
     
     
         28 . The method of  claim 26  wherein the linker group is (CH 2 ) n  where n is an integer of 1, 2, 3, or 4, (CH 2 ) 3 CO, 
       
         
           
           
               
               
           
         
       
     
     
         29 . The method of  claim 27  wherein the mixture is sonicated and heated to boiling.