Gene Therapy for Cobalamin C Deficiency (cblC) with Viable Mouse Models

Cobalamin C deficiency (cblC) is the most common inborn error of intracellular cobalamin metabolism and is caused by mutations in MMACHC, a gene responsible for processing and trafficking dependent enzymes: intracellular cobalamin, resulting in elevated methylmalonic acid and homocysteine and methionine deficiency. Disease manifestations include growth failure, anemia, cardial defects and progressive blindness. NHGRI scientist have generated the first viable mouse models of cblC using TALEN mediated genome editing and created two specific mutants of MMACHC that manifested the cblC-related biochemical perturbations. AAV vectors, and new genes, such as the synthetic and tagged MMACHC genes have also been developed that may enable gene therapy treatment for vision loss experienced by the cblC patients and possibly engender substantial commercial interest. Results of pre-clinical efficacy studies demonstrate a promising therapy for cblC disorders.