AMINO LIPIDS AND METHODS FOR THE DELIVERY OF NUCLEIC ACIDS

摘要

The present invention provides superior compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target proteins 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. An amino lipid having the following structure (II):or salts thereof, wherein
R1 and R2 are either the same or different and independently optionally substituted C12-C24 alkyl, optionally substituted C12-C24 alkenyl, optionally substituted C12-C24 alkynyl, or optionally substituted C12-C24 acyl; R3 and R4 are either the same or different and independently optionally substituted C1-C6 alkyl, optionally substituted C1C6 alkenyl, or optionally substituted C1C6 alkynyl, or R3 and R4 may join to form an optionally substituted heterocyclic ring of 4 to 6 carbon atoms and 1 or 2 heteroatoms chosen from nitrogen and oxygen; R5 is either absent or is hydrogen or C1C6 alkyl to provide a quaternary amine; m, n, and p are either the same or different and independently either 0 or 1 with the proviso that m, n, and p are not simultaneously 0; Y and Z are either the same or different and independently O, S, or NH.