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    • 3. 发明申请
    • EXPRESSION OF MODIFIED GLYCOPROTEINS AND GLYCOPEPTIDES
    • 修饰的糖蛋白和糖肽的表达
    • WO2018085273A1
    • 2018-05-11
    • PCT/US2017/059304
    • 2017-10-31
    • SYNTHETIC GENOMICS, INC.
    • CAIAZZA, Nicky, C.
    • C12N1/19C12N15/09C12N15/80C12P21/00
    • The present invention provides recombinant cells that contain a modification causing altered expression or function of at least one mannosyl transferase enzyme. As a result of the modification the cells produce a glycoprotein or glycopeptide that has an N-linked glycan profile that is simplified or humanized. The glycoprotein or glycopeptide can have at least 25% fewer high mannose structures on than the glycoprotein or glycopeptide produced by a cell that does not have the modification. In some embodiments the modification is a deletion, knock out, or disruption of a gene encoding a mannosyl transferase, which can be in an Alg3 gene. Therefore, the proteins produced avoid many of the problems associated with the therapeutic use of glycoproteins from species having foreign or plant-like patterns of glycosylation. The invention also provides compositions of the glycoproteins or glycopeptides and methods of making them.
    • 本发明提供了含有引起至少一种甘露糖基转移酶的表达或功能改变的修饰的重组细胞。 作为修饰的结果,细胞产生具有简化或人源化的N-连接的聚糖谱的糖蛋白或糖肽。 糖蛋白或糖肽可以具有比不具有修饰的细胞产生的糖蛋白或糖肽少至少25%的高甘露糖结构。 在一些实施方案中,修饰是编码甘露糖基转移酶的基因的缺失,敲除或破坏,所述甘露糖基转移酶可位于Alg3基因中。 因此,所产生的蛋白质避免了许多与具有外来或植物样糖基化模式的物种的糖蛋白的治疗用途有关的问题。 本发明还提供了糖蛋白或糖肽的组合物及其制备方法。