Composition for suppressing expression of target gene
View Patent ↗An object of the present invention is to provide a composition for suppressing expression of a target gene, and the like. A composition comprising an RNA-encapsulated liposome, wherein the RNA contains a sequence consisting of 15 to 30 contiguous bases of a target gene mRNA (hereinafter, sequence X) and a base sequence (hereinafter, complementary sequence X′) complementary to the sequence X, 1 to 90% of all sugars binding to the bases of the sequence X and the complementary sequence X′ being ribose substituted by a modifying group at 2′ position, and the lipid particle being capable of reaching a tissue or an organ containing an expression site of the target gene is provide.
1. A method for improving blood RNA concentration after a second administration to a mammal of a composition comprising a RNA-encapsulated lipid particle comprising a polyethylene glycolated lipid, a polyethylene glycol sorbitan fatty acid ester or a polyethylene glycol fatty acid ester, wherein the RNA comprises a sequence X consisting of 15 to 30 contiguous bases of a target gene mRNA and a base sequence X′ complementary to the sequence X, comprising twice administering to a mammal the composition
wherein 10 to 75% of all sugars in the RNA binding to the bases of the sequence X and the base sequence X′ are ribose substituted by a modifying group selected from the group consisting of 2′-fluoro, 2′-O-methyl, 2′-O-ethyl.
2. The method according to claim 1 , wherein the lipid particle is a lipid particle having a size that allows intravenous administration.
3. The method according to claim 2 , wherein the RNA is an RNA having an action of suppressing the expression of the target gene by utilizing RNA interference (RNAi).
4. The method according to claim 3 , wherein the target gene is a gene associated with a tumor or inflammation.
5. The method according to claim 3 , wherein the mRNA is either human mRNA or mouse mRNA.
6. The method according to claim 3 , wherein the RNA-encapsulated lipid particle comprises:
a complex particle that contains a lead particle and the RNA as constituent components, and
a lipid bilayer membrane for coating the complex particle,
wherein constituent components of the lipid bilayer membrane are soluble in a polar organic solvent, and wherein the constituent components of the lipid bilayer membrane, and the complex particle are dispersible in a liquid that contains the polar organic solvent in a specific concentration.
7. The method according to claim 6 , wherein the polar organic solvent is an alcohol.
8. The method according to claim 6 , wherein the polar organic solvent is ethanol.
9. The method according to claim 6 , wherein the lead particle contains a cationic substance, and wherein the lipid bilayer membrane contains, as constituent components, a neutral lipid, and a lipid derivative, a fatty acid derivative, or an aliphatic hydrocarbon derivative of a water-soluble substance.
10. The method according to claim 3 , wherein the RNA-encapsulated lipid particle is a lipid particle that comprises: a complex particle that contains a cationic substance-containing lead particle and the RNA as constituent components, and a lipid bilayer membrane for coating the complex particle, and
wherein the lipid bilayer membrane contains, as constituent components, a neutral lipid, and a lipid derivative, a fatty acid derivative, or an aliphatic hydrocarbon derivative of a water-soluble substance.