Nucleotide-Cochleate Compositions And Methods Of Use

Abstract

The present invention is directed to cochleate composition that include a nucleotide. The nucleotide may generally be bound via a linker to a component of the cochleate, or to a lipophilic tail. Additionally or alternatively, the nucleotide may be associated with a transfection agent. The present invention also includes methods for making and using the compositions provided herein.

1 . (canceled) 
     
     
         2 . A nucleotide-cochleate composition comprising:
 a cochleate; and   a nucleotide associated with the cochleate;   wherein the nucleotide is bound to a lipophilic tail via a linker.   
     
     
         3 . The composition of  claim 2 , wherein the linker is lipophilic or hydrophobic. 
     
     
         4 . The composition of  claim 2 , wherein the linker stabilizes the nucleotide. 
     
     
         5 . The composition of  claim 2 , wherein the linker facilitates association of the nucleotide with the cochleate component. 
     
     
         6 . The composition of  claim 2 , wherein the cochleate comprises a negatively charged lipid component and a multivalent cation component. 
     
     
         7 . The composition of  claim 2 , wherein the cochleate comprises soy phosphatidylserine. 
     
     
         8 . The composition of  claim 2 , wherein the linker is digestible, reducible, or otherwise reversible. 
     
     
         9 . The composition of  claim 2 , wherein the linker is N-succinimidyl-4-(p-maleimidophenyl)butyrate (SMPB). 
     
     
         10 . The composition of  claim 2 , wherein the linker is N-hydroxysuccinimidyl 3-(2-pyridyldithio) propionate (SPDP). 
     
     
         11 . The composition of  claim 2 , wherein the nucleotide is an siRNA. 
     
     
         12 . The composition of  claim 2 , wherein the nucleotide is a morpholino oligonucleotide. 
     
     
         13 . The composition of  claim 12 , wherein the morpholino oligonucleotide is an antisense morpholino oligonucleotide. 
     
     
         14 . The composition of  claim 2 , wherein the nucleotide is a short double-stranded DNA. 
     
     
         15 . The composition of  claim 2 , wherein the nucleotide is a ribozyme. 
     
     
         16 . The composition of  claim 2 , wherein the nucleotide is an aptamer. 
     
     
         17 . The composition of  claim 2 , wherein the nucleotide is a transcription factor decoy. 
     
     
         18 . The composition of  claim 2 , wherein the nucleotide comprises at least one mismatch. 
     
     
         19 . The composition of  claim 2 , wherein the nucleotide comprises at least one substitution. 
     
     
         20 . The composition of  claim 2 , wherein the nucleotide is about 18-25 nucleotides long. 
     
     
         21 . The composition of  claim 2 , wherein the nucleotide is about 21-23 nucleotides long. 
     
     
         22 . The composition of  claim 2 , wherein the nucleotide mediates RNA interference against a target mRNA. 
     
     
         23 . The composition of  claim 22 , wherein the target mRNA expresses a protein selected from the group consisting of: a cancer protein, a virus protein, an HIV protein, a fungus protein, a bacterial protein, an abnormal cellular protein, and a normal cellular protein. 
     
     
         24 . The composition of  claim 2 , wherein the nucleotide mediates inhibition of translation of a target mRNA. 
     
     
         25 . The composition of  claim 24 , wherein the target mRNA expresses a protein selected from the group consisting of: a cancer protein, a virus protein, an HIV protein, a fungus protein, a bacterial protein, an abnormal cellular protein, and a normal cellular protein. 
     
     
         26 . The composition of  claim 2 , further comprising a second nucleotide directed against a second target mRNA. 
     
     
         27 . The composition of  claim 2 , wherein the nucleotide is complexed with a transfection agent prior to contacting the liposomes. 
     
     
         28 . The composition of  claim 27 , wherein the transfection agent is a polycationic transfection agent. 
     
     
         29 . The composition of  claim 27 , wherein the transfection agent is polyethylenimine (PEI), protamine, or a derivative thereof. 
     
     
         30 . (canceled) 
     
     
         31 . A method of administering a nucleotide to a host comprising: administering a biologically effective amount of a nucleotide-cochleate composition according to  claim 2  to a host. 
     
     
         32 . A method of treating a subject having a disease or disorder associated with expression of a target mRNA, comprising: administering to a subject a therapeutically effective amount of an nucleotide-cochleate composition, comprising a cochleate and a nucleotide directed against a target mRNA associated with a disease or disorder, wherein the nucleotide is bound to a lipophilic tail via a linker, such that the disease or disorder is treated. 
     
     
         33 . A nucleotide-cochleate composition comprising:
 a cochleate; and   a nucleotide associated with the cochleate;   wherein the nucleotide is complexed with a transfection agent.   
     
     
         34 . The composition of  claim 33 , wherein the transfection agent is a polycationic transfection agent. 
     
     
         35 . The composition of  claim 33 , wherein the transfection agent is polyethylenimine (PEI), protamine, or derivatives thereof. 
     
     
         36 . The composition of  claim 33 , wherein the nucleotide complexed with the transfection agent is associated with the cochleate or a lipid tail via a linker. 
     
     
         37 . The composition of  claim 33 , wherein the nucleotide is an siRNA. 
     
     
         38 . The composition of  claim 33 , wherein the nucleotide is a morpholino oligonucleotide. 
     
     
         39 . The composition of  claim 38 , wherein the morpholino oligonucleotide is an antisense morpholino oligonucleotide. 
     
     
         40 . The composition of  claim 33 , wherein the nucleotide is a short double-stranded DNA. 
     
     
         41 . The composition of  claim 33 , wherein the nucleotide is a ribozyme. 
     
     
         42 . The composition of  claim 33 , wherein the nucleotide is an aptamer. 
     
     
         43 . The composition of  claim 33 , wherein the nucleotide is a transcription factor decoy. 
     
     
         44 . The composition of  claim 33 , wherein the nucleotide comprises at least one mismatch. 
     
     
         45 . The composition of  claim 33 , wherein the nucleotide comprises at least one substitution. 
     
     
         46 . The composition of  claim 33 , wherein the nucleotide is about 18-25 nucleotides long. 
     
     
         47 . The composition of  claim 33 , wherein the nucleotide is about 21-23 nucleotides long. 
     
     
         48 . The composition of  claim 33 , wherein the nucleotide mediates RNA interference against a target mRNA. 
     
     
         49 . The composition of  claim 48 , wherein the target mRNA expresses a protein selected from the group consisting of: a cancer protein, a virus protein, an HIV protein, a fungus protein, a bacterial protein, an abnormal cellular protein, and a normal cellular protein. 
     
     
         50 . The composition of  claim 33 , wherein the nucleotide mediates inhibition of translation of a target mRNA. 
     
     
         51 . The composition of  claim 50 , wherein the target mRNA expresses a protein selected from the group consisting of: a cancer protein, a virus protein, an HIV protein, a fungus protein, a bacterial protein, an abnormal cellular protein, and a normal cellular protein. 
     
     
         52 . The composition of  claim 33 , further comprising a second nucleotide directed against a second target mRNA. 
     
     
         53 . (canceled) 
     
     
         54 . A method of administering a nucleotide to a host comprising: administering a biologically effective amount of a nucleotide-cochleate composition according to  claim 33  to a host. 
     
     
         55 . A method of treating a subject having a disease or disorder associated with expression of a target mRNA, comprising: administering to a subject a therapeutically effective amount of a nucleotide-cochleate composition, comprising a cochleate and a nucleotide directed against a target mRNA associated with a disease or disorder, wherein the nucleotide is complexed to a transfection-agent, such that the disease or disorder is treated.