PXD038783 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A Universal GlycoDesign for Lysosomal Replacement Enzymes to Improve Circulation Time and Biodistribution |
Description | Currently available enzyme replacement therapies for lysosomal storage diseases are limited in their effectiveness due in part to short circulation times and suboptimal biodistribution of the therapeutic enzymes. We previously engineered Chinese hamster ovary (CHO) cells to produce -galactosidase A (GLA) with various N-glycan structures and demonstrated that elimination of mannose-6-phosphate (M6P) and conversion to homogeneous sialylated N-glycans prolonged circulation time and improved biodistribution of the enzyme following a single-dose infusion into Fabry mice. Here, we confirmed these findings using repeated infusions of the glycoengineered GLA into Fabry mice and further tested whether this glycoengineering approach, Long-Acting-GlycoDesign (LAGD), could be implemented on other lysosomal enzymes. LAGD-engineered CHO cells stably expressing a panel of lysosomal enzymes [aspartylglucosamine (AGA), beta-glucuronsidase (GUSB), catepsin D (CTSD), tripeptidyl peptidase (TPP1), alpha-glucosidase (GAA) or iduronate 2-sulfatase (IDS)] successfully converted all M6P-containing N-glycans to complex sialylated N-glycans. The resulting homogenous glycodesigns enabled glycoprotein profiling by native mass spectrometry. Notably, LAGD extended the plasma half-life of all three enzymes tested (GLA, GUSB, AGA) in wildtype mice. LAGD may be widely applicable to lysosomal replacement enzymes to improve their circulatory stability and therapeutic efficacy. |
HostingRepository | PRIDE |
AnnounceDate | 2023-02-13 |
AnnouncementXML | Submission_2023-02-13_03:26:04.508.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | SergeyVakhrushev |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos; Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-12-12 22:57:24 | ID requested | |
⏵ 1 | 2023-02-13 03:26:04 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Glycoproteomics, LC-Ms, Therapeutics, OrbiTrap |
Contact List
SergeyVakhrushev |
contact affiliation | Department of Cellular and Molecular Medicine, University of Copenhagen |
contact email | seva@sund.ku.dk |
lab head | |
SergeyVakhrushev |
contact affiliation | Department of Cellular and Molecular Medicine |
contact email | seva@sund.ku.dk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/02/PXD038783 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD038783
- Label: PRIDE project
- Name: A Universal GlycoDesign for Lysosomal Replacement Enzymes to Improve Circulation Time and Biodistribution