RETROVIRAL-MEDIATED GENE-THERAPY FOR THE TREATMENT OF CITRULLINEMIA -TRANSFER AND EXPRESSION OF ARGININOSUCCINATE SYNTHETASE IN HUMAN HEMATOPOIETIC-CELLS

Citrullinemia is a recessive genetic disease caused by a deficiency in argininosuccinate synthetase (AS). Retroviruses were used to transduc e the human AS gene into cultured human cells. Using amphotropic virus es with high titer (> 10(6) cfu/ml), we were able to correct the defec t in cultured fibroblasts from citrullinemic patients. Retroviral tran sduction of the human AS gene into human bone marrow cells was also st udied. Co-cultivation was used to infect the cells and up to 80% of pr ogenitor cells were found to be carrying and expressing the AS retrovi rus after infection. When the infected cells were kept in culture, int egration and expression of the retrovirus was observed. Retroviral seq uences were present and expressed in the cultured bone marrow-derived cells for up to 10 weeks.