Cationic lipids and methods for the delivery of therapeutic agents

摘要

The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel cationic lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid in vivo. The compositions of the present invention are highly potent, thereby allowing effective know-down of a specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

主权项

1. A cationic lipid of Formula VIII having the following structure:or salts thereof, wherein:
R1 and R2 are either the same or different and are independently an optionally substituted C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl, or R1 and R2 may join to form an optionally substituted heterocyclic ring of 4 to 6 carbon atoms and 1 or 2 heteroatoms selected from the group consisting of nitrogen (N), oxygen (O), and mixtures thereof; R3 is either absent or is hydrogen (H) or a C1-C6 alkyl to provide a quaternary amine; R4, R5, and R6 are either the same or different and are independently an optionally substituted C12-C24 alkyl, C12-C24 alkenyl, C12-C24 alkynyl, or C12-C24 acyl; and n is 0, 1, 2, 3, or 4.