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PXD013140

PXD013140 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe Glycosylation Design Space for Recombinant Lysosomal Replacement Enzymes Produced in CHO Cells
DescriptionLysosomal storage diseases are rare life-threatening disorders caused by deficiency of a lysosomal enzyme, and delivery of a recombinant replacement enzyme is the primary therapy for several of these diseases. The structures of N-glycans on recombinant replacement enzymes are important for their therapeutic efficacy, biodistribution and circulation time. Here we use alpha-galactosidase A (GLA) and beta-glucoscerebrosidase (GBA) as representative replacement enzymes, and present a panel of genetically engineered CHO cells that enable production of lysosomal replacement enzymes with different N-glycan features. We also tested several GLA variants with distinct glycoforms in a Fabry mouse model and present evidence that GLA glycoforms capped with alpha 2-3 linked sialic acids may represent a new strategy to overcome the most critical problems of rapid clearance in liver and poor biodistribution found with current ERTs.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:06:34.996.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSergey Vakhrushev
SpeciesList scientific name: Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); NCBI TaxID: 10029; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListcomplex glycosylation
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-03-19 03:10:53ID requested
12019-05-31 06:02:14announced
22024-10-22 04:06:39announced2024-10-22: Updated project metadata.
Publication List
10.1038/s41467-019-09809-3;
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, The glycosylation design space for recombinant lysosomal replacement enzymes produced in CHO cells. Nat Commun, 10(1):1785(2019) [pubmed]
Keyword List
submitter keyword: N-glycoproteomics, enzyme replacement therapy,Glycoengineering
Contact List
Henrik Clausen
contact affiliationCopenhagen Center for Glycomics (CCG), Department of Cellular and Molecular Medicine, University of Copenhagen
contact emailhclau@sund.ku.dk
lab head
Sergey Vakhrushev
contact affiliationDepartment of Cellular and Molecular Medicine
contact emailseva@sund.ku.dk
dataset submitter
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Dataset FTP location
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PRIDE project URI
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