| abstract |
The present disclosure relates to mRNA therapeutic agents for the treatment of propionic acidemia (PA). The mRNA used in the present invention, when administered in vivo, is human propionyl CoA carboxylase alpha (PCCA) and / or human propionyl CoA carboxylase beta (PCCB), and its isoforms, functional fragments thereof, and PCCA and / or PCCB. Encodes a fusion protein containing. The mRNA of the present invention is preferably encapsulated in lipid nanoparticles (LNPs) in a subject so as to provide efficient delivery to cells and / or tissues when administered thereto. The mRNA treatment of the present invention increases and / or restores the expression and / or activity level of deficient propionyl-CoA carboxylase (PCC) in a subject. The mRNA treatment of the present invention further reduces the levels of disease-related toxic metabolites associated with deficient PCCA or PCCB activity in the subject. |