Lipid nanoparticles

A lipid nanoparticle comprising:

• an ionizable lipid;
• from about 5 mol % to about 15 mol % of a phospholipid selected from the group consisting of DOPE, DOPC, and mixtures thereof;
• a sterol;
• a PEG lipid;
• and
• one or more nucleic acid molecules,
• wherein the lipid nanoparticle has a minimal average diameter of about 140 nm.

A method for the preparation of nucleic acid-containing lipid nanoparticles having a minimal average diameter of about 140 nm, the method comprising:

• preparing a first alcoholic composition comprising an ionizable lipid, a phospholipid, a sterol, a PEG lipid, and an alcoholic solvent;
• preparing a second aqueous composition comprising one or more nucleic acids and an aqueous solvent supplemented with a buffer;
• mixing the first alcoholic composition and the second aqueous composition in a microfluidic mixing device using the following settings:
• a Total Flow Rate (FR) from about 0.5 mL/min to about 8 mL/min;
• and
• a Flow Rate Ratio (FRR) from about 1/1 to 5/1.