Genetically modified mouse models to help fight COVID-19.

Genetically modified mouse models to help fight COVID-19.
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DOI:
10.1038/s41596-020-00403-2
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发表时间:
2020-12
期刊:
影响因子:
14.8
通讯作者:
Ohtsuka M
Ohtsuka M
中科院分区:
生物学1区
文献类型:
--
作者:
Gurumurthy CB;Quadros RM;Richardson GP;Poluektova LY;Mansour SL;Ohtsuka M

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研究界正在竞相了解SARS-CoV-2感染的分子机制,重新利用现有的抗病毒药物,并开发针对COVID-19的新疗法和疫苗。实现这些目标的一个主要挑战是缺乏合适的临床前动物模型。在生物医学研究中使用的所有实验动物中,小鼠约占70%。不幸的是,SARS-CoV-2只有在经过基因改造以表达人类ACE2的情况下才会感染小鼠。野生型小鼠对SARS-CoV-2的固有抵抗力,加上大量仅用于修饰小鼠的遗传工具,为创建一套可用于COVID-19研究的通用基因工程小鼠模型(gemm)提供了独特的机会。我们提出了这些模型的三大类和二十多种设计,这些设计可能对SARS-CoV-2研究和对抗COVID-19有用。在这一视角中,作者讨论了创建一套可用于COVID-19研究的30种通用基因工程小鼠模型(gemm)的策略。此外,它们还提供了开发这些gem所需的基因蓝图。
The research community is in a race to understand the molecular mechanisms of SARS-CoV-2 infection, to repurpose currently available antiviral drugs, and to develop new therapies and vaccines against COVID-19. One major challenge in achieving these goals is the paucity of suitable preclinical animal models. Mice constitute around 70 percent of all of laboratory animal species used in biomedical research. Unfortunately, SARS-CoV-2 only infects mice if they have been genetically modified to express human ACE2. The inherent resistance of wild-type mice to SARS-CoV-2, combined with a wealth of genetic tools that are only available for modifying mice, offer a unique opportunity to create a versatile set of genetically engineered mouse models (GEMMs) useful for COVID-19 research. We propose three broad categories of these models and more than two dozen designs that may be useful for SARS-CoV-2 research and for fighting COVID-19. In this Perspective, the authors discuss strategies for creating a versatile set of 30 genetically engineered mouse models (GEMMs) useful for COVID-19 research. Additionally, they provide the genetic blueprints needed for developing these GEMMs.
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