Composition and methods for the pulmonary delivery of nucleic acids
View Patent ↗The present invention relates to compositions and methods for the pulmonary delivery of nucleic acids, particularly oligonucleotides. In one preferred embodiment, the compositions and methods of the invention are utilized to effect the pulmonary delivery of an antisense oligonucleotide to an animal in order to modulate the expression of a gene in the animal for investigative, therapeutic or prophylactic purposes.
1. A method for enhancing cellular uptake of an oligonucleotide administered as an aerosol into a lung of a mammal by including 2′-O-methoxyethyl and 5-methylcytosine modifications in said oligonucleotide, said method comprising:
administering an aerosolized oligonucleotide into the lung of a mammal,
wherein the aerosol particles have a size of about 1 to about 5 microns, wherein said oligonucleotide is 15 to 25 nucleotides in length, wherein at least 10 nucleosides in said oligonucleotide are 2′-O-methoxyethyl nucleosides, wherein each cytosine of said oligonucleotide is a 5-methylcytosine, and wherein said oligonucleotide is taken up by at least one cell type in the lung of the mammal.
2. The method of claim 1 , wherein at least one internucleotide linkage within said oligonucleotide is a phosphorothioate linkage.
3. The method of claim 1 , wherein said oligonucleotide is in an aqueous media.
4. The method of claim 1 , wherein said oligonucleotide is in sterilized, pyrogen free water.
5. The method of claim 1 , wherein said oligonucleotide is in a saline solution.
6. The method of claim 1 , wherein said oligonucleotide is in a powder.
7. The method of claim 1 , wherein each internucleotide linkage within said oligonucleotide is a phosphorothioate linkage.
8. The method of claim 1 , wherein said oligonucleotide is 20 nucleotides in length, and said oligonucleotide is in a saline solution.
9. The method of claim 8 , wherein each internucleotide linkage within said oligonucleotide is a phosphorothioate linkage.
10. The method of claim 8 , wherein each nucleoside in said oligonucleotide is a 2′-O-methoxyethyl nucleoside.
11. The method of claim 1 , wherein at least 10 to all but one nucleosides in said oligonucleotide are 2′-O-methoxyethyl nucleosides.