生物信息学
计算机科学
药物发现
药物开发
计算生物学
下垂
生化工程
过程(计算)
药品
生物
生物信息学
工程类
药理学
生物化学
考古
操作系统
基因
历史
作者
Adriana-Michelle Wolf Pérez,Nikolai Lorenzen,Michele Vendruscolo,Pietro Sormanni
出处
期刊:Methods in molecular biology
日期:2021-09-04
卷期号:: 57-113
被引量:26
标识
DOI:10.1007/978-1-0716-1450-1_4
摘要
Although antibodies have become the fastest-growing class of therapeutics on the market, it is still challenging to develop them for therapeutic applications, which often require these molecules to withstand stresses that are not present in vivo. We define developability as the likelihood of an antibody candidate with suitable functionality to be developed into a manufacturable, stable, safe, and effective drug that can be formulated to high concentrations while retaining a long shelf life. The implementation of reliable developability assessments from the early stages of antibody discovery enables flagging and deselection of potentially problematic candidates, while focussing available resources on the development of the most promising ones. Currently, however, thorough developability assessment requires multiple in vitro assays, which makes it labor intensive and time consuming to implement at early stages. Furthermore, accurate in vitro analysis at the early stage is compromised by the high number of potential candidates that are often prepared at low quantities and purity. Recent improvements in the performance of computational predictors of developability potential are beginning to change this scenario. Many computational methods only require the knowledge of the amino acid sequences and can be used to identify possible developability issues or to rank available candidates according to a range of biophysical properties. Here, we describe how the implementation of in silico tools into antibody discovery pipelines is increasingly offering time- and cost-effective alternatives to in vitro experimental screening, thus streamlining the drug development process. We discuss in particular the biophysical and biochemical properties that underpin developability potential and their trade-offs, review various in vitro assays to measure such properties or parameters that are predictive of developability, and give an overview of the growing number of in silico tools available to predict properties important for antibody development, including the CamSol method developed in our laboratory.
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