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哺乳动物展示技术在治疗性抗体开发及其他领域的进展:现状、挑战与未来展望。

Advancements in mammalian display technology for therapeutic antibody development and beyond: current landscape, challenges, and future prospects.

机构信息

Discovery & Engineering Division, Iontas Ltd./FairJourney Biologics, Cambridge, United Kingdom.

Technology Division, Iontas/FairJourney Biologics, Cambridge, United Kingdom.

出版信息

Front Immunol. 2024 Sep 24;15:1469329. doi: 10.3389/fimmu.2024.1469329. eCollection 2024.

DOI:10.3389/fimmu.2024.1469329
PMID:39381002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11459229/
Abstract

The evolving development landscape of biotherapeutics and their growing complexity from simple antibodies into bi- and multi-specific molecules necessitates sophisticated discovery and engineering platforms. This review focuses on mammalian display technology as a potential solution to the pressing challenges in biotherapeutic development. We provide a comparative analysis with established methodologies, highlighting key aspects of mammalian display technology, including genetic engineering, construction of display libraries, and its pivotal role in hit selection and/or developability engineering. The review delves into the mechanisms underpinning developability-driven selection via mammalian display and their broader implications. Applications beyond antibody discovery are also explored, alongside advancements towards function-first screening technologies, precision genome engineering and AI/ML-enhanced libraries, situating them in the context of mammalian display. Overall, the review provides a comprehensive overview of the current mammalian display technology landscape, underscores the expansive potential of the technology for biotherapeutic development, addresses the critical challenges for the full realisation of this potential, and examines advances in related disciplines that might impact the future application of mammalian display technologies.

摘要

生物疗法的不断发展的领域及其从简单抗体向双特异性和多特异性分子的日益复杂,需要复杂的发现和工程平台。本文重点介绍哺乳动物展示技术作为解决生物疗法开发中紧迫挑战的潜在解决方案。我们与已建立的方法进行了比较分析,突出了哺乳动物展示技术的关键方面,包括遗传工程、展示文库的构建,以及其在命中选择和/或可开发性工程中的关键作用。本文深入探讨了通过哺乳动物展示实现可开发性驱动选择的机制及其更广泛的影响。除了抗体发现之外,还探讨了该技术的其他应用,以及朝着功能优先筛选技术、精确基因组工程和 AI/ML 增强文库的进展,将它们置于哺乳动物展示的背景下。总的来说,本文全面概述了当前哺乳动物展示技术的现状,强调了该技术在生物疗法开发中的广泛潜力,解决了充分实现这一潜力的关键挑战,并探讨了相关学科的进展,这些进展可能会影响哺乳动物展示技术的未来应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5a6/11459229/fe2db8c2813c/fimmu-15-1469329-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5a6/11459229/fe2db8c2813c/fimmu-15-1469329-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5a6/11459229/ade0976c915f/fimmu-15-1469329-g001.jpg
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