Abstract: This disclosure relates to mRNA therapy for the treatment of hyperphenylalaninemias such as phenylketonuria (PKU). mRNAs for use in the invention, when administered in vivo, encode human phenylalanine hydroxylase (PAH), functional fragments thereof (e.g., those comprising the catalytic domain or the catalytic domain and the tetramerization domains), and fusion proteins comprising PAH. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of PAH expression and/or activity in subjects. mRNA therapies of the invention further decrease abnormal accumulation of phenylalanine associated with deficient PAH activity in subjects.

Abstract: A cooling system includes a heat sink to absorb heat that is generated by a component of a device, where the heat sink includes a base to dissipate the heat, and a group of fins via which the heat, that is dissipated by the base, is transferred; and an inverted heat sink to receive the heat via the fins. The inverted heat sink includes another base to prevent a portion of the heat, transferred into an environment where another component is located, from causing a temperature, of the environment, to increase above a threshold; a heat pipe to transfer another portion of the heat, not transferred into the environment, to a portion of the other base; and another group of fins to receive the other portion of the heat via the portion of the other base. The inverted heat sink is also to transfer the other portion of the heat to another environment to prevent a temperature, of the component, from increasing above another threshold.