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.
Rommerskirch
W
W
Universität Göttingen, Abteilung Biochemie II, Federal Republic of Germany.
Fluharty
A L
AL
Peters
C
C
von Figura
K
K
Gieselmann
V
V
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