METABOLIC CORRECTION OF CONGENITAL ERYTHROPOIETIC PORPHYRIA BY RETROVIRUS-MEDIATED GENE-TRANSFER INTO EPSTEIN-BARR-VIRUS TRANSFORMED B-CELLLINES

Congenital erythropoietic porphyria (CEP) is an inherited metabolic di sorder resulting from the accumulation of porphyrins because of defect ive uroporphyrinogen III synthase (UROIIIS). This autosomal recessive disorder is phenotypically heterogeneous with respect to the age of on set and the severity of the symptoms. Different exonic point mutations in the UROIIIS gene have been identified, providing phenotype-genotyp e correlations in this disease. Severe cases may be treated by bone ma rrow transplantation and are potential candidates for somatic gene the rapy. Epstein-Barr virus-transformed B-cell lines from patients with C EP provide a model system for the disease. We have used retrovirus-med iated expression of UROIIIS to restore enzymatic activity in a B-cell line from a patient. We have also demonstrated the metabolic correctio n of the disease, ie, porphyrin accumulation into the deficient transd uced cells was reduced to the normal level. These data show the potent ial of gene therapy for this disease. (C) 1995 by The American Society of Hematology.