DRY POWDER COMPOSITIONS FOR RNA INFLUENZA THERAPEUTICS
A dry powder formulation for delivery to a mammal by inhalation, the formulation comprising particles comprising a lipid, a carrier, and one or more double-stranded siRNA molecules or dicer-active precursors targeted to influenza virus A method for treating or preventing influenza in a mammal comprising administering a therapeutically-effective amount of a dry powder formulation.
1 . A dry powder formulation for delivery to a mammal by inhalation, the formulation comprising particles comprising a lipid, a carrier, and one or more double-stranded siRNA molecules or dicer-active precursors targeted to influenza virus, wherein the formulation silences influenza virus by 81-99%.
2 . The formulation of claim 1 , wherein the one or more siRNAs are targeted to a plurality of influenza virus strains.
3 . The formulation of claim 1 , wherein the one or more siRNAs are targeted to two or more regions of the same influenza virus transcript.
4 . The formulation of claim 1 , wherein at least one of the siRNAs has at least one 5-methyluridine-containing nucleotide.
5 . The formulation of claim 1 , further comprising calcium chloride.
6 . The formulation of claim 1 , further comprising albumin or protamine.
7 . The formulation of claim 1 , further comprising arginine or leucine.
8 . The formulation of claim 1 , wherein the lipid is selected from the group of dipalmitoylethylphosphocholine, dioleoyl phosphatidylethanolamine, 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol, 1,2-dioleoyl-sn-glycero-3-[phospho-L-serine], 1,2-dioleoyl-sn-glycero-3-phosphate, 1,2-dioleoyl-sn-glycero-3-phosphocholine, distearoylphosphatidylcholine, diarachidoylphosphatidylcholin, dipalmitoyl phosphatidylethanolamine, and mixtures thereof.
9 . The formulation of claim 1 , wherein the lipid is 1,2-dipalmitoyl-sn-glycero-3-phosphocholine.
10 . The formulation of claim 1 , wherein the particles have an MMAD of from about 1 to 6 μm.
11 . The formulation of claim 1 , wherein the fine particle fraction (FPF) of the powder is from about 20 to about 70%.
12 . The formulation of claim 1 , wherein the purity of the siRNA is greater than about 90% by weight upon storage at 25° C. for a period of 18 months.
13 . A method for treating influenza in a mammal comprising administering a therapeutically-effective amount of the formulation of claim 1 to the mammal.
14 . A method for preventing influenza in a mammal comprising administering a therapeutically-effective amount of the formulation of claim 1 to the mammal.