Nucleic acid-containing lipid nanoparticles

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,
• R4 to R6, the same or different, are a linear or branched, and either unsubstituted or substituted C8-C24 alkyl, C8-C24 alkenyl or C8-C24 alkynyl,
• L4 to L6, the same or different, are absent or are —Z4—(CY8Y9)p4— or —Z5—(CY10Y11)p5—Z6—(CY12Y13)p6— (wherein, Y8 to Y13, the same or different, are a hydrogen atom or optionally substituted C1-C4 alkyl, Z4 to Z6, the same or different, are —O—, —NY14A—, —CO—O—, —O—CO—, —CO—NY14B—, —NY4C—CO— or (wherein, Y14A to Y14D the same or different, are a hydrogen atom or optionally substituted C1-C4 alkyl), p4 is an integer of 0 to 5, p5 is an integer of 1 to 5, and p6 is an integer of 0 to 5),
• L7 is (CY15Y16)p7—, —(CY17Y18)p8—Z7—(CY19Y20)p9— —(CY21Y22)p10—Z8—(CY23Y24)p11—Z9—(CY25Y26)p12— (wherein, Y15 to Y26, the same or different, are a hydrogen atom or optionally substituted C1-C4 alkyl, Z7 to Z9, the same or different, are —O—, —NY27A—, —CO—O—, or —O—CO—, (wherein, Y27A, the same or different, is a hydrogen atom or optionally substituted C1-C4 alkyl), p7 is an integer of 1 to 5, p8 is an integer of 0 to 5, p9 is an integer of 1 to 5, p10 is an integer of 0 to 5, p11 is an integer of 1 to 5, and p12 is an integer of 1 to 5),
• B1 is
• (wherein, X2 and X3, 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, X4 is an optionally substituted C1-C4 alkyl, X5 and X6, 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, X7 is an optionally substituted C1-C4 alkyl, Y28 to Y37, the same or different, are a hydrogen atom or optionally substituted C1-C4 alkyl, Z10 and Z11, the same or different, are —O—, —NY38A—, —OO—O—, —O—CO—, —CO—NY38B, —NY38C—CO— or —NY38D—CO—O— (wherein, Y38A to Y38D, the same or different, are a hydrogen atom or optionally substituted C1-C4 alkyl), p13 is an integer of 0 to 5, and p14 to p17, the same or different, are an integer of 1 to 5), and
• A2 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.