The emerging field of biotherapeutics provides successful treatments for various diseases, yet immunogenicity and limited efficacy remain major concerns for many products. Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity. Hence, an increased attention is directed at optimizing the glycosylation properties of biotherapeutics. Currently, most biotherapeutics are produced in non-human mammalian cells in light of their ability to produce human-like glycosylation. However, most mammals produce the sialic acid N-glycolylneuraminic acid (Neu5Gc), while humans cannot due to a specific genetic defect. Humans consume Neu5Gc in their diet from mammalian derived foods (red meat and dairy) and produce polyclonal antibodies against diverse Neu5Gc-glycans. Moreover, Neu5Gc can metabolically incorporate into human cells and become presented on surface or secreted glycans, glycoproteins, and glycolipids. Several studies in mice suggested that the combination of Neu5Gc-containing epitopes and anti-Neu5Gc antibodies could contribute to exacerbation of chronic inflammation-mediated diseases (e.g., cancer, cardiovascular diseases, and autoimmunity). This could potentially become complicated with exposure to Neu5Gc-containing biotherapeutics, bio-devices or xenografts. Indeed, Neu5Gc can be found on various approved and marketed biotherapeutics. Here, we provide a perspective review on the possible consequences of Neu5Gc glycosylation of therapeutic protein drugs due to the limited published evidence of Neu5Gc glycosylation on marketed biotherapeutics and studies on their putative effects on immunogenicity, drug efficacy, and safety.

中文翻译：

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糖基化生物疗法：N-糖基神经氨酸的免疫学作用。

生物治疗学的新兴领域为各种疾病提供了成功的治疗方法，但是免疫原性和有限的功效仍然是许多产品关注的主要问题。糖基化是决定生物治疗药理学特性的关键因素，包括其稳定性，溶解性，生物利用度，药代动力学和免疫原性。因此，人们越来越关注优化生物治疗药物的糖基化性质。当前，大多数生物治疗药物由于其产生人样糖基化的能力而在非人哺乳动物细胞中产生。但是，大多数哺乳动物会产生唾液酸N-羟乙酸神经氨酸（Neu5Gc），而人类则不会由于特定的遗传缺陷而产生这种唾液酸。人类在饮食中从哺乳类食品（红肉和奶制品）中摄取Neu5Gc，并产生针对多种Neu5Gc聚糖的多克隆抗体。此外，Neu5Gc可以代谢整合到人体细胞中，并呈现在表面或分泌的聚糖，糖蛋白和糖脂上。小鼠中的多项研究表明，含Neu5Gc的抗原决定簇和抗Neu5Gc抗体的组合可能会加剧慢性炎症介导的疾病（例如，癌症，心血管疾病和自身免疫性）。暴露于含Neu5Gc的生物治疗剂，生物装置或异种移植物可能会使情况变得复杂。确实，Neu5Gc可以在各种批准的和市售的生物治疗剂中找到。这里，