Methods and compositions for regulation of metabolic disorders

A cell comprising an exogenous transgene encoding a protein, wherein the exogenous transgene is integrated site-specifically using a nuclease into an endogenous safe harbor gene and further wherein the protein is a functional version of a protein that is aberrantly expressed in a metabolic disorder selected from the group consisting of methylmalonic acidemia, propionic acidemia, glycogen storage diseases type 1, familial hypercholesterolemia (FH) is a common genetic and metabolic disease, urea cycle disorders, Crigler Najjar Syndrome (CNS), Gilbert syndrome, hepatorenal tyrosinemia, primary hyperoxaluria. transthyretin gene (TTR)-mediated amyloidosis (ATTR), Wilson's disease, phenylketonuria (PKU), and familial lipoprotein lipase deficiency (LPLD).