The present invention provides, among other things, compositions and methods of formulating nucleic acid-containing nanoparticles comprising no more than three distinct lipids components, one distinct lipid component being a sterol-based cationic lipid. In some embodiments, the present invention provides compositions and methods in which the lipid nanoparticles further comprise helper lipids and PEG-modified lipids. The resulting formulation comprises a high encapsulation percentage for nucleic acids.La presente invencion proporciona, entre otras cosas, composiciones y metodos para formular nanoparticulas que contienen acidos nucleicos que comprenden no mas de tres componentes de lipidos distintos, un componente lipidico distinto que es un lipido cationico basado en esteroles； en algunas modalidades, la presente invencion proporciona composiciones y métodos en los cuales las nanoparticulas lipidicas comprenden ademas lipidos auxiliares y lipidos modificados con PEG； la formulacion resultante comprende un porcentaje de encapsulacion alto de acidos nucleicos.
