Multicellular Systems to Translate Somatic Cell Genome Editors to Humans.
Multicellular Systems to Translate Somatic Cell Genome Editors to Humans.
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DOI：
10.1016/j.cobme.2020.100249
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发表时间：
2020-12
影响因子：
3.9
通讯作者：
Kiani S
中科院分区：
文献类型：
--
作者：
Hernandez-Gordillo V;Casolaro TC;Ebrahimkhani MR;Kiani S
随着基因组编辑器进入临床试验，需要建立离体多细胞系统，以快速评估和预测基因组编辑器在生理相关人类模型中的毒性作用。类器官和芯片上器官技术的进步为创建复制天然组织的细胞组成和代谢功能的多细胞系统提供了可能性。一些多细胞系统已经在药物发现的多种应用中得到验证，并且可以很容易地适应于测试基因组编辑器;其他模型，特别是适应性免疫系统的模型，在用作测试基因组编辑器的基准之前需要验证。同样，需要建立和验证评估免疫原性、检测脱靶效应以及预测离体到体内翻译的方案。本文将讨论在设计、构建和/或采用体外人类多细胞系统测试基因组编辑器时需要考虑的关键方面。
As genome editors move into clinical trials, there is a need to establish ex vivo 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 ex vivo to in vivo translation will need to be established and validated. This review will discuss key aspects to consider when designing, building, and/or adopting in vitro human multicellular systems for testing genome editors.
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