SENS PubMed Publication Search
The glycosylation design space for recombinant lysosomal replacement enzymes produced in CHO cells.
Tian W, Ye Z, Wang S, Schulz MA, Van Coillie J, Sun L, Chen YH, Narimatsu Y, Hansen L, Kristensen C, Mandel U, Bennett EP, Jabbarzadeh-Tabrizi S, Schiffmann R, Shen JS, Vakhrushev SY, Clausen H, Yang Z
Abstract:
...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 selected glycoforms of α-galactosidase A in a Fabry disease mouse model, and find that an α2-3 sialylated glycoform designed to eliminate uptake by the mannose 6-phosphate and mannose receptors exhibits improved circulation time and targeting to hard-to-reach organs such as heart. The developed design matrix and engineered CHO cell lines enables systematic studies towards improving enzyme replacement therapeutics.
PMID: 31040271
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491494/
SENS Approach:
