Polynucleotides encoding propionyl-coa carboxylase alpha and beta subunits for the treatment of propionic acidemia

A method of treating propionic academia in a human subject in need thereof, the method comprising administering to the human subject by intravenous infusion a pharmaceutical composition comprising lipid nanoparticles comprising:

• (1) a first messenger RNA (mRNA) comprising a first open reading frame (ORF) encoding the human propionyl-CoA carboxylase alpha (PCCA) polypeptide of SEQ ID NO:1, wherein the first ORF is at least 80% identical to the nucleotide sequence of SEQ ID NO:5, and (2) a second mRNA comprising a second ORF encoding the human propionyl-CoA carboxylase beta (PCCB) polypeptide of SEQ ID NO:2, wherein the second ORF is at least 80% identical to the nucleotide sequence of SEQ ID NO:6, wherein the first mRNA and the second mRNA are present in the lipid nanoparticles at a ratio of 1:1, and wherein the first mRNA and the second mRNA are administered to the human subject at a combined dose of about 0.3 mg/kg to about 1.0 mg/kg.