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CC BY-NC-ND V4.0, Open Access
Journal article
Enhanced α2-3 linked sialylation determines the extended half-life of CHO-rVWF
Blood, Vol.145(23)
2025
PMID: 40101144
Abstract
[Display omitted]
The half-life of recombinant von Willebrand factor (rVWF) expressed in CHO cells (CHO-rVWF; Vonicog alfa; and Vonvendi/Veyvondi) is significantly longer than that of plasma-derived VWF (pdVWF) concentrates. This finding is intriguing because CHO cells do not generate α2-6 sialylation, which constitutes the majority of human pdVWF sialylation. We hypothesized that glycan differences might regulate the longer half-life of CHO-rVWF. In lectin plate-binding assays and liquid chromatography–mass spectrometry analysis, we confirmed that CHO-rVWF lacked α2-6 linked sialylation. Conversely, however, α2-3 linked sialylation was significantly increased on CHO-rVWF, which also had reduced exposed β-Gal compared to pdVWF. Consistent with human data, CHO-rVWF clearance was significantly (P < .001) reduced in VWF–/– mice compared to pdVWF. However, clearance of asialo-pdVWF and asialo–CHO-rVWF were identical. In keeping with the in vivo half-life prolongation, CHO-rVWF binding to murine macrophages (P = .012) and HepG2 cells (P = .001) was significantly decreased compared to pdVWF. Furthermore, CHO-rVWF binding to purified macrophage-galactose-type lectin (MGL) receptor and asialoglycoprotein receptor (ASGPR) was also significantly reduced. In contrast to pdVWF, in vivo studies in MGL1–/– mice and Asgr1–/– mice demonstrated that neither MGL nor ASGPR plays significant roles in regulating CHO-rVWF clearance. Together, our findings demonstrate that enhanced α2-3 linked sialylation on CHO-rVWF is responsible for its extended in vivo half-life.
Details
- Title
- Enhanced α2-3 linked sialylation determines the extended half-life of CHO-rVWF
- Authors/Creators
- Ciara Byrne - Royal College of Surgeons in IrelandSoracha Ward - Royal College of Surgeons in IrelandJamie O’Sullivan - Royal College of Surgeons in IrelandAlain Chion - Royal College of Surgeons in IrelandPatricia Lopes - Royal College of Surgeons in IrelandBogdan Baci - Royal College of Surgeons in IrelandCaoimhe Dowd - Royal College of Surgeons in IrelandDarragh Jordan - Royal College of Surgeons in IrelandRoss Baker - Murdoch University, Centre for Molecular Medicine and Innovative TherapeuticsRoger J.S. Preston - Royal College of Surgeons in IrelandMarco Monopoli - Royal College of Surgeons in IrelandPeter L. Turecek - Takeda (Austria)Maximilianos Kotsias - Ludger (United Kingdom)Jack Cheeseman - Ludger (United Kingdom)Alan B. Moran - Culham Science CentreRichard A. Gardner - Culham Science CentreDaniel I.R. Spencer - Ludger (United Kingdom)Ferdows Atiq - Royal College of Surgeons in IrelandJames S. O’Donnell - Royal College of Surgeons in Ireland
- Publication Details
- Blood, Vol.145(23)
- Publisher
- Elsevier Inc
- Number of pages
- 6
- Identifiers
- 991005765131607891
- Copyright
- © 2025 American Society of Hematology
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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