Dept. Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, United States.
Dept. of Chemical Engineering & Materials Science, Michigan State University, East Lansing, MI 48824, United States; Dept. of Biosystems Engineering, Michigan State University, East Lansing, MI 48824, United States; Dept. of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, United States; Institute for Quantitative Biology, Michigan State University, East Lansing, MI 48824, United States.
Curr Opin Biotechnol. 2019 Dec;60:104-110. doi: 10.1016/j.copbio.2019.01.015. Epub 2019 Feb 26.
Protein therapeutics requires a series of properties beyond biochemical activity, including serum stability, low immunogenicity, and manufacturability. Mutations that improve one property often decrease one or more of the other essential requirements for therapeutic efficacy, making the protein engineering challenge difficult. The past decade has seen an explosion of new techniques centered around cheaply reading and writing DNA. This review highlights the recent use of such high throughput technologies for engineering protein therapeutics. Examples include the use of human antibody repertoire sequence data to pair antibody heavy and light chains, comprehensive mutational analysis for engineering antibody specificity, and the use of ancestral and inter-species sequence data to engineer simultaneous improvements in enzyme catalytic efficiency and stability. We conclude with a perspective on further ways to integrate mature protein engineering pipelines with the exponential increases in the volume of sequencing data expected in the forthcoming decade.
蛋白质疗法需要一系列超越生化活性的特性，包括血清稳定性、低免疫原性和可制造性。改善一种特性的突变往往会降低治疗效果的其他一个或多个基本要求，这使得蛋白质工程的挑战变得困难。过去十年，出现了一系列以廉价读取和编写 DNA 为中心的新技术。本综述强调了最近使用这些高通量技术来工程蛋白质疗法的情况。例如，使用人类抗体库序列数据来配对抗体的重链和轻链，全面的突变分析用于工程抗体特异性，以及使用祖先和种间序列数据来同时提高酶的催化效率和稳定性。最后，我们展望了在未来十年测序数据量预计呈指数级增长的情况下，如何进一步将成熟的蛋白质工程管道与测序数据相结合。
