Hernandez-Gordillo Victor, Casolaro Thomas Caleb, Ebrahimkhani Mo R, Kiani Samira
Department of Pathology, Division of Experimental Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA.
Curr Opin Biomed Eng. 2020 Dec;16:72-81. doi: 10.1016/j.cobme.2020.100249. Epub 2020 Oct 10.
As genome editors move into clinical trials, there is a need to establish multicellular systems to rapidly assess and predict toxic effects of genome editors in physiologically relevant human models. Advancements in organoid and organs-on-chip technologies offer the possibility to create multicellular systems that replicate the cellular composition and metabolic function of native tissues. Some multicellular systems have been validated in multiple applications for drug discovery and could be easily adapted to test genome editors; other models, especially those of the adaptive immune system, will require validation before being used as benchmarks for testing genome editors. Likewise, protocols to assess immunogenicity, to detect off-target effects, and to predict translation will need to be established and validated. This review will discuss key aspects to consider when designing, building, and/or adopting human multicellular systems for testing genome editors.
随着基因组编辑技术进入临床试验阶段，需要建立多细胞系统，以便在生理相关的人类模型中快速评估和预测基因组编辑的毒性作用。类器官和芯片器官技术的进步为创建能够复制天然组织细胞组成和代谢功能的多细胞系统提供了可能性。一些多细胞系统已在药物发现的多个应用中得到验证，并且可以轻松地用于测试基因组编辑技术；其他模型，尤其是适应性免疫系统的模型，在用作测试基因组编辑技术的基准之前需要进行验证。同样，评估免疫原性、检测脱靶效应以及预测转化的方案也需要建立和验证。本综述将讨论在设计、构建和/或采用用于测试基因组编辑技术的人类多细胞系统时需要考虑的关键方面。
