Gene Therapy for Propionic Acidemia

Propionic acidemia (PA) is a metabolic genetic disease that occurs in 1 in 35,000 live births in United States and up to 1 in 3,000 in Saudi Arabia. This disease causes metabolic acidosis, ketosis, vomiting, lethargy, mental retardation, and death. This metabolic decompensation occurs in response to the consumption of normal levels of proteins in the diet, but can also be precipitated by other stimuli. PA is caused by deficiency in either the alpha or beta subunits of the mitochondrial enzyme propionyl CoA carboxylase (PCC), encoded by the PCCA and PCCB genes. Since there is currently no cure for PA, this project is testing gene therapy to correct this disease using adenoviral and adeno-associated virus (AAV) vectors. This project involves vector detargeting and retargeting and stealthing the viruses from the immune system.