TY - JOUR
T1 - Characterization of Human Recombinant N-Acetylgalactosamine-6-Sulfate Sulfatase Produced in Pichia pastoris as Potential Enzyme for Mucopolysaccharidosis IVA Treatment
AU - Rodríguez-López, Alexander
AU - Pimentel-Vera, Luisa N.
AU - Espejo-Mojica, Angela J.
AU - Van Hecke, Annelies
AU - Tiels, Petra
AU - Tomatsu, Shunji
AU - Callewaert, Nico
AU - Alméciga-Díaz, Carlos J.
N1 - Publisher Copyright:
© 2019 American Pharmacists Association®
PY - 2019/8
Y1 - 2019/8
N2 - Mucopolysaccharidosis IVA (MPS IVA or Morquio A syndrome) is a lysosomal storage disease caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to lysosomal storage of keratan sulfate and chondroitin-6-sulfate. Currently, enzyme replacement therapy using an enzyme produced in CHO cells represents the main treatment option for MPS IVA patients. As an alternative, we reported the production of an active GALNS enzyme produced in the yeast Pichia pastoris (prGALNS), which showed internalization by cultured cells through a potential receptor-mediated process and similar post-translational processing as human enzyme. In this study, we further studied the therapeutic potential of prGALNS through the characterization of the N-glycosylation structure, in vitro cell uptake and keratan sulfate reduction, and in vivo biodistribution and generation of anti-prGALNS antibodies. Taken together, these results represent an important step in the development of a P. pastoris–based platform for production of a therapeutic GALNS for MPS IVA enzyme replacement therapy.
AB - Mucopolysaccharidosis IVA (MPS IVA or Morquio A syndrome) is a lysosomal storage disease caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to lysosomal storage of keratan sulfate and chondroitin-6-sulfate. Currently, enzyme replacement therapy using an enzyme produced in CHO cells represents the main treatment option for MPS IVA patients. As an alternative, we reported the production of an active GALNS enzyme produced in the yeast Pichia pastoris (prGALNS), which showed internalization by cultured cells through a potential receptor-mediated process and similar post-translational processing as human enzyme. In this study, we further studied the therapeutic potential of prGALNS through the characterization of the N-glycosylation structure, in vitro cell uptake and keratan sulfate reduction, and in vivo biodistribution and generation of anti-prGALNS antibodies. Taken together, these results represent an important step in the development of a P. pastoris–based platform for production of a therapeutic GALNS for MPS IVA enzyme replacement therapy.
KW - GALNS
KW - Morquio A
KW - Pichia pastoris
KW - glycosylations
KW - mucopolysaccharidosis IV A
UR - http://www.scopus.com/inward/record.url?scp=85064674654&partnerID=8YFLogxK
U2 - 10.1016/j.xphs.2019.03.034
DO - 10.1016/j.xphs.2019.03.034
M3 - Article
C2 - 30959056
AN - SCOPUS:85064674654
SN - 0022-3549
VL - 108
SP - 2534
EP - 2541
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 8
ER -
