NUCLEOTIDE-COCHLEATE COMPOSITIONS AND METHODS OF USE
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 he 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;
a lipophilic tail; and
a siRNA associated with the cochleate;
wherein the siRNA is complexed with a transfection agent and covalently bound to N-hydroxysuccinimidyl 3-(2-pyridyldithio)propionate (SPDP), and
wherein the SPDP is covalently bound to the lipophilic tail.
3 . (canceled)
4 . The composition of claim 2 , wherein the SPDP stabilizes the siRNA.
5 . The composition of claim 2 , wherein the SPDP facilitates association of the siRNA 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 . (canceled)
9 . The composition of claim 2 , wherein the linker is N-succinimidyl-4-(p-maleimidophenyl)butyrate (SMPB).
10 - 11 . (canceled)
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 siRNA comprises at least one mismatch.
19 . The composition of claim 2 , wherein the siRNA comprises at least one substitution.
20 . The composition of claim 2 , wherein the siRNA is between about 18 and about 25 nucleotides long.
21 . The composition of claim 2 , wherein the siRNA is between about 21 and about 23 nucleotides long.
22 . The composition of claim 2 , wherein the siRNA 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 siRNA 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 siRNA is complexed with a transfection agent prior to contacting a 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 - 37 . (canceled)
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 - 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.