Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
GlycoDisplay ApS, Copenhagen, Denmark.
Nat Commun. 2024 Nov 8;15(1):9668. doi: 10.1038/s41467-024-53738-9.
Access to defined glycans and glycoconjugates is pivotal for discovery, dissection, and harnessing of a range of biological functions orchestrated by cellular glycosylation processes and the glycome. We previously employed genetic glycoengineering by nuclease-based gene editing to develop sustainable production of designer glycoprotein therapeutics and cell-based glycan arrays that display glycans in their natural context at the cell surface. However, access to human glycans in formats and quantities that allow structural studies of molecular interactions and use of glycans in biomedical applications currently rely on chemical and chemoenzymatic syntheses associated with considerable labor, waste, and costs. Here, we develop a sustainable and scalable method for production of glycans in glycoengineered mammalian cells by employing secreted Glycocarriers with repeat glycosylation acceptor sequence motifs for different glycans. The Glycocarrier technology provides a flexible production platform for glycans in different formats, including oligosaccharides, glycopeptides, and multimeric glycomodules, and offers wide opportunities for use in bioassays and biomedical applications.
获得特定的糖链和糖缀合物对于发现、剖析和利用细胞糖基化过程和糖组所调控的一系列生物学功能至关重要。我们之前采用基于核酸酶的基因编辑进行遗传糖工程，以实现设计的糖蛋白治疗药物和基于细胞的糖链阵列的可持续生产，这些药物和阵列在细胞表面以天然状态展示糖链。然而，目前获得适合于分子相互作用结构研究和在生物医学应用中使用的糖链，仍然依赖于与大量劳动、浪费和成本相关的化学和化学酶合成。在这里，我们通过使用具有不同糖链重复糖基化接受序列基序的分泌性 Glycocarrier，开发了一种在糖工程化哺乳动物细胞中生产糖链的可持续和可扩展的方法。Glycocarrier 技术为不同形式的糖链（包括寡糖、糖肽和多聚体糖模块）提供了灵活的生产平台，并为生物测定和生物医学应用提供了广泛的应用机会。
