Lipid particle, nucleic acid transfer carrier, compound for manufacturing nucleic acid transfer carrier, method for manufacturing lipid particle, and gene transfer method

摘要

The present invention provides a lipid particle which has low cytotoxicity, can stably hold a nucleic acid molecule outside a cell (in blood), and can escape from an endosome and rapidly release the nucleic acid in the cytoplasm; a nucleic acid transfer carrier; a compound for manufacturing a nucleic acid transfer carrier; a method for manufacturing a lipid particle; and a gene transfer method. The lipid particle contains, as constituents, a phospholipid having one or more amino groups and one or more nitrogen-containing heterocyclic groups, a neutral lipid not containing a nitrogen-containing heterocyclic group, a sterol, and a nucleic acid.

主权项

1. A lipid particle comprising, as constituents:
a phospholipid having one or more amino groups and one or more nitrogen-containing heterocyclic groups; a neutral lipid not containing a nitrogen-containing heterocyclic group; a sterol; and a nucleic acid, wherein the phospholipid having one or more amino groups and one or more nitrogen-containing heterocyclic groups is a lipid represented by the following Formula (I) or a salt thereof, in Formula (I), X represents an oxygen atom or a sulfur atom; Y represents a hydrophobic group; each of W and V independently represents a single bond, —O—, —NH—, —CO—, or a linking group as a combination of these; each of R1 and R2 independently represents a hydrogen atom or an alkoxycarbonyl group having 1 to 4 carbon atoms; each of R3 and R4 independently represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyalkyl group having 1 to 4 carbon atoms, an alkoxycarbonyl group having 1 to 4 carbon atoms, an aminoalkyl group having 1 to 4 carbon atoms, a guanidinoalkyl group having 1 to 4 carbon atoms, or an imidazolylalkyl group having 4 to 7 carbon atoms; each of R5 and R6 independently represents a hydrogen atom, an amino group, or an alkoxycarbonyl group having 1 to 4 carbon atoms; when n is 1, at least one of R5 and R6 represents an amino group; when n is an integer from 2 to 4, at least one of the plural R5s and plural R6s contained in Formula (I) represents an amino group; l represents an integer from 2 to 4; m represents an integer from 0 to 4; and n represents an integer from 1 to 4.