Abstract: The instant disclosure relates to nucleic acid-lipid particles that mix ionizable and cationic lipids, which preferentially localize and deliver associated cargoes to the liver when administered parenterally, and which optionally can be used to deliver associated cargoes to tissues to which such particles are directly injected. The instant disclosure provides compositions comprising such lipid particles, optionally in association with a therapeutic agent (e.g., a therapeutic mRNA and/or nucleic acid controller system), as well as methods and kits for delivering a lipid particle-associated therapeutic agent and/or treating a disease or disorder, e.g., a liver disease or disorder, in a subject, using the lipid particle compositions provided herein.

Abstract: The instant disclosure relates to nucleic acid-lipid particles having 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), which preferentially localize and deliver associated cargoes to the lung and various lung tissues, as well as to tissues to which such particles are directly injected. The instant disclosure provides compositions comprising such lipid particles, optionally in association with a therapeutic agent (e.g., a therapeutic mRNA and/or nucleic acid controller system), as well as methods and kits for delivering a lipid particle-associated therapeutic agent and/or treating a disease or disorder, e.g., a lung disease or disorder, in a subject, using the lipid particle compositions provided herein.