COMPOSITIONS AND METHODS FOR COMPLEXES OF NUCLEIC ACIDS AND ORGANIC CATIONS
What is described is a stable double stranded (ds) nucleic acid molecule composition, comprising a dsRNA molecule complexed with an organic cation.
1 . A method for producing a complex between a double stranded (ds) nucleic acid and an organic salt, comprising:
a. solubilizing the nucleic acid in an aqueous solution, wherein the nucleic acid is present with a first counterion;
b. mixing the solubilized nucleic acid with an organic salt; and
c. separating the nucleic acid from the first counterion.
2 . The method of claim 1 , wherein the ds nucleic acid is a dsRNA.
3 . The method of claim 2 , wherein the dsRNA is siRNA.
4 . The method of claim 3 , wherein siRNA has 19-50 base pairs.
5 . The method of claim 4 , wherein siRNA is comprised of a sequence that is complementary to a region of a TNF-alpha gene.
6 . The method of claim 1 , wherein the ds nucleic acid is a dsDNA.
7 . The method of claim 1 , wherein the organic salt is an organic cation.
8 . The method of claim 7 , wherein the organic cation is selected from the group consisting of: ammonium hydroxide, D-arginine, L-arginine, t-butylamine, calcium acetate hydrate, calcium carbonate, calcium DL-malate, calcium hydroxide, choline, ethanolamine, ethylenediamine, glycine, L-histidine, L-lysine, magnesium hydroxide, N-methyl-D-glucamine, L-ornithine hydrochloride, potassium hydroxide, procaine hydrochloride, L-proline, pyridoxine, L-serine, sodium hydroxide, DL-triptophan, tromethamine, L-tyrosine, L-valine, carnitine, taurine, creatine malate, arginine alpha keto glutarate, ornithine alpha keto glutarate, spermine acetate, and spermidine chloride.
9 . The method of claim 7 , wherein the organic cation is selected from the group consisting of N-methyl D-glucamine, choline, arginine, lysine, procaine, tromethamine (TRIS), spermine, N-methyl-morpholine, glucosamine, N,N-bis 2-hydroxyethyl glycine, diazabicycloundecene, creatine, arginine ethyl ester, amantadine, rimantadine, ornithine, taurine, and citrulline.
10 . A stable double stranded (ds) nucleic acid molecule composition, comprising a dsRNA molecule complexed with an organic salt.
11 . The composition of claim 10 , wherein the dsRNA is siRNA.
12 . The composition of claim 10 , wherein siRNA has 19-50 base pairs.
13 . The composition of claim 12 , wherein siRNA is comprised of a sequence that is complementary to a region of a TNF-alpha gene.
14 . The composition of claim 10 , wherein the ds nucleic acid is a dsDNA.
15 . The composition of claim 10 , wherein the organic salt is selected from the group consisting of sugar amines and acids, peptide amines and acids, biocompatible salts, hydrophilic salts, and salts naturally occurring in man.
16 . The composition of claim 10 , wherein the organic salt is an organic cation.
17 . The composition of claim 16 , wherein the organic cation is selected from the group consisting of: ammonium hydroxide, D-arginine, L-arginine, t-butylamine, calcium acetate hydrate, calcium carbonate, calcium DL-malate, calcium hydroxide, choline, ethanolamine, ethylenediamine, glycine, L-histidine, L-lysine, magnesium hydroxide, N-methyl-D-glucamine, L-ornithine hydrochloride, potassium hydroxide, procaine hydrochloride, L-proline, pyridoxine, L-serine, sodium hydroxide, DL-triptophan, tromethamine, L-tyrosine, L-valine, camitine, taurine, creatine malate, arginine alpha keto glutarate, ornithine alpha keto glutarate, spermine acetate, and spermidine chloride.
18 . The composition of claim 16 , wherein the organic cation is selected from the group consisting of N-methyl D-glucamine, choline, arginine, lysine, procaine, tromethamine (TRIS), spermine, N-methyl-morpholine, glucosamine, N,N-bis 2-hydroxyethyl glycine, diazabicycloundecene, creatine, arginine ethyl ester, amantadine, rimantadine, ornithine, taurine, and citrulline.
19 . A stable double stranded (ds) nucleic acid molecule composition, comprising a dsRNA molecule complexed with an organic salt, wherein the composition is produced by:
a. solubilizing the nucleic acid in an aqueous solution, wherein the nucleic acid is present with a first counterion;
b. mixing the solubilized nucleic acid with an organic salt; and
c. separating the nucleic acid from the first counterion.
20 . The composition of claim 19 , wherein the dsRNA is siRNA.
21 . The composition of claim 19 , wherein siRNA has 19-50 base pairs.
22 . The composition of claim 21 , wherein siRNA is comprised of a sequence that is complementary to a region of a TNF-alpha gene.
23 . The composition of claim 19 , wherein the ds nucleic acid is a dsDNA.
24 . The composition of claim 19 , wherein the organic salt is selected from the group consisting of sugar amines and acids, peptide amines and acids, biocompatible salts, hydrophilic salts, and salts naturally occurring in man.
25 . The composition of claim 19 , wherein the organic salt is an organic cation.
26 . The composition of claim 25 , wherein the organic cation is selected from the group consisting of: ammonium hydroxide, D-arginine, L-arginine, t-butylamine, calcium acetate hydrate, calcium carbonate, calcium DL-malate, calcium hydroxide, choline, ethanolamine, ethylenediamine, glycine, L-histidine, L-lysine, magnesium hydroxide, N-methyl-D-glucamine, L-ornithine hydrochloride, potassium hydroxide, procaine hydrochloride, L-proline, pyridoxine, L-serine, sodium hydroxide, DL-triptophan, tromethamine, L-tyrosine, L-valine, camitine, taurine, creatine malate, arginine alpha keto glutarate, ornithine alpha keto glutarate, spermine acetate, and spermidine chloride.
27 . The composition of claim 25 , wherein the organic cation is selected from the group consisting of N-methyl D-glucamine, choline, arginine, lysine, procaine, tromethamine (TRIS), spermine, N-methyl-morpholine, glucosamine, N,N-bis 2-hydroxyethyl glycine, diazabicycloundecene, creatine, arginine ethyl ester, amantadine, rimantadine, ornithine, taurine, and citrulline.