Restoration of arylsulphatase A activity in human-metachromatic-leucodystrophy fibroblasts via retroviral-vector-mediated gene transfer.
Metachromatic leukodystrophy is a lysosomal storage disease caused by the deficiency of arylsulphatase A (ASA). A human ASA cDNA was subcloned into the retroviral vector pXT1. Replication-defective retrovirus was generated by transfection of the vector into the amphotropic packaging cell line PA317. Human fibroblasts from a patient suffering from metachromatic leucodystrophy was infected with the recombinant retrovirus. Infected fibroblasts expressed ten times more ASA compared with control fibroblasts from a normal individual. The ASA encoded by the integrated provirus was shown to be correctly transported into the lysosomes and to normalize the impaired degradation of cerebroside sulphate.
Universität Göttingen, Abteilung Biochemie II, Federal Republic of Germany.
W
W
Rommerskirch
A L
AL
Fluharty
C
C
Peters
K
K
von Figura
V
V
Gieselmann
D002458:Cell Fractionation; D002460:Cell Line; D002553:Cerebroside-Sulfatase / Q000235:genetics / Q000378:metabolism*; D002554:Cerebrosides / Q000378:metabolism; D004247:DNA / Q000235:genetics; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D006868:Hydrolysis; D007966:Leukodystrophy, Metachromatic / Q000201:enzymology*; D011233:Precipitin Tests; D012190:Retroviridae / Q000235:genetics*; D014162:Transfection
D002554:Cerebrosides; D004247:DNA; D002553:Cerebroside-Sulfatase