Anti-doping Lab-Qatar, Research Department, Protein Engineering unit, Doha, Qatar; Drug Design Group, Department of Pharmacy, University of Groningen, Antonius Deusinglaan, AV, Groningen, the Netherlands.
Xi'an Jiaotong-Liverpool University, Department of Biological Sciences, Science and Education Innovation District, Suzhou, 215123, China.
Biomed Pharmacother. 2019 May;113:108750. doi: 10.1016/j.biopha.2019.108750. Epub 2019 Mar 5.
Protein therapeutics play a significant role in treating many diseases. They, however, suffer from patient's proteases degradation and antibody neutralization which lead to short plasma half-lives. One of the ways to overcome these pitfalls is the frequent injection of the drug albeit at the cost of patient compliance which affects the quality of life of patients. There are several techniques available to extend the half-life of therapeutics. Two of the most common protocols are PEGylation and fusion with human serum albumin. These two techniques improve stability, reduce immunogenicity, and increase drug resistance to proteases. These factors lead to the reduction of injection frequency which increases patient compliance and improve quality of life. Both techniques have already been used in many FDA approved drugs. This review describes many technologies to produce long-acting drugs with the attention of PEGylation and the genetic fusion with human serum albumin. The report also discusses the latest modified therapeutics in the field and their application in cancer therapy. We compare the modification methods and discuss the pitfalls of these modified drugs.
蛋白质疗法在治疗许多疾病方面发挥着重要作用。然而,它们会受到患者蛋白酶的降解和抗体中和的影响,导致血浆半衰期较短。克服这些困难的方法之一是频繁注射药物,尽管这会降低患者的依从性,从而影响患者的生活质量。有几种技术可用于延长治疗药物的半衰期。其中两种最常见的方法是聚乙二醇化和与人血清白蛋白融合。这两种技术可提高稳定性、降低免疫原性,并增加对蛋白酶的耐药性。这些因素导致注射频率降低,从而提高了患者的依从性并改善了生活质量。这两种技术已经在许多获得 FDA 批准的药物中得到应用。本综述描述了许多生产长效药物的技术,重点介绍了聚乙二醇化和与人血清白蛋白的基因融合。该报告还讨论了该领域最新的修饰治疗药物及其在癌症治疗中的应用。我们比较了修饰方法,并讨论了这些修饰药物的缺陷。