McGonigle Paul
Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA; email:
Annu Rev Pharmacol Toxicol. 2025 Jan;65(1):29-46. doi: 10.1146/annurev-pharmtox-061724-080811. Epub 2024 Dec 17.
Advances in molecular biology and molecular genetics as well as major scientific breakthroughs in immunology and oncology have led to the rapid growth of biologic therapeutics. Their success has resulted in significant changes to virtually every step in the drug discovery and development process. Biologics are produced by living organisms, and screening libraries are generated by immunization or phage display. Lead optimization utilizes sophisticated protein engineering to improve drug-like properties and targeting specificity. The manufacturing process for biologics is complex and requires highly specialized facilities. Determination of pharmacology and safety must overcome the complications associated with species specificity. Initial clinical testing must proceed more slowly and carefully due to the limited predictive utility of preclinical data. In summary, the drug discovery and development process has been dramatically altered by biologic therapeutics and will continue to evolve with the introduction of messenger RNA-based therapeutics and the application of artificial intelligence.
分子生物学和分子遗传学的进展以及免疫学和肿瘤学的重大科学突破推动了生物疗法的迅速发展。它们的成功几乎给药物研发过程中的每一个环节都带来了重大变化。生物制品由活生物体生产，筛选文库通过免疫或噬菌体展示产生。先导优化利用复杂的蛋白质工程来改善类药性质和靶向特异性。生物制品的生产过程复杂，需要高度专业化的设施。药理学和安全性的测定必须克服与物种特异性相关的复杂性。由于临床前数据的预测效用有限，初始临床试验必须更缓慢、更谨慎地进行。总之，生物疗法极大地改变了药物研发过程，并且随着基于信使核糖核酸的疗法的引入和人工智能的应用，这一过程将继续演变。
