InVivo Biosystems, Eugene, OR, United States.
Mayo Clinic, Rochester, MN, United States.
J Mol Biol. 2021 May 14;433(10):166945. doi: 10.1016/j.jmb.2021.166945. Epub 2021 Mar 20.
The COVID-19 pandemic entered its third and most intense to date wave of infections in November 2020. This perspective article describes how combination therapies (polytherapeutics) are a needed focus for helping battle the severity of complications from SARS-CoV-2 infection. It outlines the types of systems that are needed for fast and efficient combinatorial assessment of therapeutic candidates. Proposed are micro-physiological systems using human iPSC as a format for tissue-specific modeling of infection, the use of gene-humanized zebrafish and C. elegans for combinatorial drug screens due to the animals being addressable in liquid multi-well formats, and the use of engineered pseudo-typing systems to safely model infection in the transgenic animals and engineered tissue systems.
2020 年 11 月，COVID-19 大流行进入了其第三波也是迄今为止最严重的感染浪潮。本文从描述性角度出发，探讨了联合治疗（多疗法）对于应对严重的 SARS-CoV-2 感染并发症的重要性，并提出了用于快速、高效的治疗候选药物组合评估所需的系统类型。文中还提出了使用人类诱导多能干细胞（iPSC）作为感染组织特异性建模的微生理系统，利用基因人源化斑马鱼和秀丽隐杆线虫进行组合药物筛选的方法，由于这些动物可以在液体多孔板格式中进行操作，因此具有优势。此外，还可以利用工程假型系统在转基因动物和工程组织系统中安全地模拟感染。
