Corrective effect on Fabry mice of yeast recombinant human alpha-galactosidase with N-linked sugar chains suitable for lysosomal delivery

Journal of Human Genetics
Hitoshi SakurabaTamotsu Kanzaki

Abstract

We have previously reported the production of a recombinant alpha-galactosidase with engineered N-linked sugar chains facilitating uptake and transport to lysosomes in a Saccharomyces cerevisiae mutant. In this study, we improved the purification procedure, allowing us to obtain a large amount of highly purified enzyme protein with mannose-6-phosphate residues at the non-reducing ends of sugar chains. The products were incorporated into cultured fibroblasts derived from a patient with Fabry disease via mannose-6-phosphate receptors. The ceramide trihexoside (CTH) accumulated in lysosomes was cleaved dose-dependently, and the disappearance of deposited CTH was maintained for at least 7 days after administration. We next examined the effect of the recombinant alpha-galactosidase on Fabry mice. Repeated intravascular administration of the enzyme led to successful degradation of CTH accumulated in the liver, kidneys, heart, and spleen. However, cleavage of the accumulated CTH in the dorsal root ganglia was insufficient. As the culture of yeast cells is easy and economical, and does not require fetal calf serum, the recombinant alpha-galactosidase produced in yeast cells is highly promising as an enzyme source for enzyme replacement...Continue Reading

References

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Citations

Jan 9, 2010·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Rafael Fernández-LeiroJuliana Sanz-Aparicio
Mar 8, 2008·Bioscience, Biotechnology, and Biochemistry·Yoshifumi Jigami
Oct 27, 2009·American Journal of Human Genetics·Youichi TajimaHitoshi Sakuraba
Feb 27, 2015·PloS One·Mariam MeghdariDavid H Calhoun
Mar 20, 2012·Molecular Genetics and Metabolism·Maria Fatima MacedoMaria Clara Sa Miranda
Jun 15, 2015·Molecular Genetics and Metabolism·Ángela J Espejo-MojicaLuis A Barrera
Apr 11, 2018·Biotechnology and Applied Biochemistry·Natalia PimentelLuis A Barrera-Avellaneda
Sep 5, 2018·Microbial Cell Factories·María-Efigenia Álvarez-CaoMaría-Isabel González-Siso
Jan 29, 2020·Archives of Pharmacal Research·Dong Hyun KimJae-Young Lee
Dec 29, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Hiroaki YonishiYoshitaka Isaka

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