The glycosylation design space for recombinant lysosomal replacement enzymes produced in CHO cells.

ABSTRACT: Lysosomal replacement enzymes are essential therapeutic options for rare congenital lysosomal enzyme deficiencies, but enzymes in clinical use are only partially effective due to short circulatory half-life and inefficient biodistribution. Replacement enzymes are primarily taken up by cell surface glycan receptors, and glycan structures influence uptake, biodistribution, and circulation time. It has not been possible to design and systematically study effects of different glycan features. Here we present a comprehensive gene engineering screen in Chinese hamster ovary cells that enables production of lysosomal enzymes with N-glycans custom designed to affect key glycan features guiding cellular uptake and circulation. We demonstrate distinct circulation time and organ distribution of selec

SUBMITTER: Tian W 

PROVIDER: S-EPMC6491494 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature