Some of the recombinant protein therapeutics with short half-life requires high frequent dose or injection, which results in poor patient compliance. This challenge has prompted the development of long-acting recombinant proteins in recent years. Four strategies and methods, including chemical modification, protein engineering, fusion proteins and protein glycosylation are used to modify protein molecule and finally obtain improved pharmacokinetics (PK) properties. This article reviews the four strategies of half-life extension and presents a detailed list of long-acting therapeutics on US, EU and China markets.
部分重组蛋白药物存在半衰期短的缺陷，临床给药频率高，且大多为注射给药，严重影响患者使用依从性。长效重组蛋白药物是近年来生物技术药物发展的重要趋势之一。对蛋白分子进行改造或修饰，延长重组蛋白药物的半衰期，实现长效以减少给药频率主要通过4种方式：化学修饰、构建突变体、蛋白融合、糖基化修饰。针对上述4种长效化方式及已上市相关产品进行了综述。展望未来，紧跟国外先进技术和质量标准发展，进一步提高国产长效重组蛋白药物质量水平，推进国内相关产品标准升级，推动创新长效重组蛋白药物开发及专利布局是未来几年国内该领域的发展方向。.
Keywords: advances; fusion protein; half-life; long-acting; modification; recombinant protein.