Lipid encapsulating interfering RNA
View Patent ↗The present invention provides lipid-based formulations for delivering, e.g., introducing, nucleic acid-lipid particles comprising an interference RNA molecule to a cell, and assays for optimizing the delivery efficiency of such lipid-based formulations.
1. A method for in vivo delivery of interfering RNA, said method comprising administering to a mammalian subject a nucleic acid-lipid particle comprising:
(a) said interfering RNA;
(b) a cationic lipid of Formula I and having the following structure:
wherein:
R 1 and R 2 are independently selected from the group consisting of: H and C 1 -C 3 alkyl; and
R 3 and R 4 are independently selected from the group consisting of alkyl groups having from about 10 to about 20 carbon atoms, wherein at least one of R 3 and R 4 comprises at least two sites of unsaturation;
(c) a non-cationic lipid; and
(d) a conjugated lipid that inhibits aggregation of particles.
2. The method of claim 1 , wherein said mammal is a human.
3. The method of claim 2 , wherein said human has a disease or disorder associated with expression of a gene and wherein expression of said gene is reduced by said interfering RNA.
4. The method of claim 3 , wherein said disease or disorder is associated with overexpression of said gene.
5. The method of claim 1 , wherein said administration is by intravenous injection at a site of administration.
6. The method of claim 5 , wherein presence of said interfering RNA at a site distal to the site of administration is detectable for at least 48 hours after administration of said particle.
7. The method of claim 5 , wherein presence of said interfering RNA at a site distal to the site of administration is detectable for at least 24 hours after administration of said particle.