Nucleic acid-containing lipid nanoparticles

1. Nucleic acid-containing lipid nanoparticles, comprising: a lipid (lipid A), which has a hydrophilic unit having a single quaternary ammonium group and three independent, substituted and either unsubstituted or substituted hydrocarbon groups; a lipid derivative or fatty acid derivative of a water-soluble polymer; and a nucleic acid,

wherein the number of moles of the quaternary ammonium group in the lipid A is 0.1 to 10 times the number of moles of phosphorous atoms in the nucleic acid,

the average particle size is 20 nm to 65 nm, and

the lipid A is a lipid represented by:

(wherein,

R 4 to R 6 , the same or different, are a linear or branched, and either unsubstituted or substituted C8-C24 alkyl, C8-C24 alkenyl or C8-C24 alkynyl,

L 4 to L 6 , the same or different, are absent or are —Z 4 —(CY 8 Y 9 ) p4 — or —Z 5 —(CY 10 Y 11 ) p5 —Z 6 —(CY 12 Y 13 ) p6 — (wherein, Y 8 to Y 13 , the same or different, are a hydrogen atom or optionally substituted C1-C4 alkyl, Z 4 to Z 6 , the same or different, are —O—, —NY 14A —, —CO—O—, —O—CO—, —CO—NY 14B —, —NY 4C —CO— or (wherein, Y 14A to Y 14D the same or different, are a hydrogen atom or optionally substituted C1-C4 alkyl), p 4 is an integer of 0 to 5, p 5 is an integer of 1 to 5, and p 6 is an integer of 0 to 5),

L 7 is (CY 15 Y 16 ) p7 —, —(CY 17 Y 18 ) p8 —Z 7 —(CY 19 Y 20 ) p9 — —(CY 21 Y 22 ) p10 —Z 8 —(CY 23 Y 24 ) p11 —Z 9 —(CY 25 Y 26 ) p12 — (wherein, Y 15 to Y 26 , the same or different, are a hydrogen atom or optionally substituted C1-C4 alkyl, Z 7 to Z 9 , the same or different, are —O—, —NY 27A —, —CO—O—, or —O—CO—, (wherein, Y 27A , the same or different, is a hydrogen atom or optionally substituted C1-C4 alkyl), p 7 is an integer of 1 to 5, p 8 is an integer of 0 to 5, p 9 is an integer of 1 to 5, p 10 is an integer of 0 to 5, p 11 is an integer of 1 to 5, and p 12 is an integer of 1 to 5),

B 1 is

(wherein, X 2 and X 3 , the same or different, are an optionally substituted C1-C4 alkyl or are combined together to form an optionally substituted C4-C6 heterocycle with an adjacent nitrogen atom, X 4 is an optionally substituted C1-C4 alkyl, X 5 and X 6 , the same or different, are an optionally substituted C1-C4 alkyl or are combined together to form an optionally substituted C4-C6 heterocycle with an adjacent nitrogen atom, X 7 is an optionally substituted C1-C4 alkyl, Y 28 to Y 37 , the same or different, are a hydrogen atom or optionally substituted C1-C4 alkyl, Z 10 and Z 11 , the same or different, are —O—, —NY 38A —, —OO—O—, —O—CO—, —CO—NY 38 B, —NY 38C —CO— or —NY 38D —CO—O— (wherein, Y 38A to Y 38D , the same or different, are a hydrogen atom or optionally substituted C1-C4 alkyl), p 13 is an integer of 0 to 5, and p 14 to p 17 , the same or different, are an integer of 1 to 5), and

A 2 is a pharmaceutically acceptable anion);

and a lipid (lipid B), which has a hydrophilic unit having one secondary or tertiary amino group or one substituted secondary or tertiary amino group, and a hydrophobic unit having two independent linear C8-C24 alkyl or alkenyl groups or two independent substituted linear C8-C24 alkyl or alkenyl groups;

wherein the ratio of the number of moles of lipid A to the number of moles of lipid B is 0.01 to 2;

wherein the nucleic acid has a molecular weight of 1,000 kDa or less.

2. The lipid nanoparticles according to claim 1 , wherein the lipid A is represented by formula (II), and in formula (II), one of L 4 to L 6 is —CO—O—(CY 8 Y 9 ) p4 —, —O—CO—(CY 8 Y 9 ) p4 — or —O—CO—(CY 10 Y 11 ) p5 —O—(CY 12 Y 13 ) p6 — or two or more of L 4 to L 6 , the same or different, are —CO—O—(CY 8 Y 9 ) p4 —, —O—CO—(CY 8 Y 9 ) p4 — or —O—CO—(CY 10 Y 11 ) p5 —O—(CY 12 Y 13 ) p6 — and), R 4 to R 6 are linear or branched C15-C20 alkenyl or C9-C18 alkyl and are the same.

3. The nucleic acid-containing lipid nanoparticles of claim 1 , wherein the number of moles of lipid A is smaller than the number of moles of lipid B.