The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include an ionizable lipid, a phospholipid, a first sterol or a tocopherol, and optionally a second sterol different from the first sterol. Nanoparticle compositions further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.
