DNA vector delivery using lipid nanoparticles

A lipid nanoparticle comprising encapsulated DNA vector and 35 to 60 mol % of a neutral lipid comprising or consisting of a phosphatidylcholine lipid, a cationic lipid at from 15 mol % to 45 mol %, at least one of a sterol and a hydrophilic polymer-lipid conjugate, and a combined sterol and neutral lipid content of at least 55 mol %, the lipid nanoparticle having an amine-to-phosphate charge ratio (N/P) from 3 to 15 and comprising a core having an electron dense region and an aqueous portion as determined by cryogenic transmission electron microscopy, the electron dense region being visualized by the cryogenic transmission electron microscopy as a dark region relative to the aqueous portion, the core surrounded at least partially by a lipid layer and the lipid nanoparticle exhibiting at least a 10% increase in DNA expression in a disease site or in the liver, spleen and/or bone marrow at any one time point greater than 24 or 48 hours post-injection as compared to a lipid nanoparticle encapsulating the DNA vector with a formulation of ionizable lipid/DSPC/cholesterol/PEG-lipid at 50/10/38.5/1.5, mol:mol, wherein the DNA expression is measured in an animal model by detection of a green fluorescent protein (GFP), wherein each mol % is based on a total lipid content in the lipid nanoparticle.