酶类药物现状、问题及展望

Therapeutic Enzymes:History,Challenges and Perspectives

随着生物制药的迅速发展,许多酶类药物应运而生,在治疗代谢疾病、心血管疾病、癌症等诸多疾病上发挥着越来越重要的作用。但是酶类药物也存在一些不足,如潜在的免疫原性、较短的体内半衰期,以及较差的组织靶向性,影响了酶类药物的疗效和应用。为克服这些缺点,人们已开发出多种技术,如通过糖基化、聚乙二醇修饰等分子工程技术提升酶蛋白药效,另一方面酶基因疗法也已成功用于多种酶缺陷疾病的治疗。基于酶类药物的迅速发展和广泛的应用前景,本文对酶类药物的现状进行较详细的阐述,并对酶类药物的优势、所存在的问题及未来发展趋势进行分析和评述。

With the development of biopharmacology,many therapeutic enzymes have been developed for treatment of various diseases,including metabolic diseases,thrombotic cardiovascular diseases and cancers.Most of the approved therapeutic enzymes are hydrolases,which are used to clean the toxic organic compounds and biomacromolecules in vivo,such as saccharides,lipids,proteins and their aggregates.Due to the high catalytic activity,affinity and specificity of enzyme towards substrate,enzyme therapy has a shorter time frame and fewer side reactions compared to other therapeutic approaches.However,there are several critical bottlenecks that limit the effectiveness of therapeutic enzymes,including immunogenicity,short circulation time,and lack of tissue specificity.Many approaches have been used to overcome these challenges.Several second generation therapeutic enzymes with significantly improved effectiveness have been developed using molecular engineering technologies such as glycan modification and pegylation.In addition,enzyme gene therapy becomes an emerging approach for treatment of diseases caused by enzymes deficiencies.Here,we reviewed the current enzyme-based therapeutics,and discussed its advantages,challenges and future perspectives.