Applications of and considerations for using CRISPR-Cas9-mediated gene conversion systems in rodents
Applications of and considerations for using CRISPR-Cas9-mediated gene conversion systems in rodents
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DOI：
10.1038/s41596-021-00646-7
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发表时间：
2021-12-23
期刊：
影响因子：
14.8
通讯作者：
Cooper, Kimberly L.
中科院分区：
文献类型：
--
作者：
Grunwald, Hannah A.;Weitzel, Alexander J.;Cooper, Kimberly L.
本视角讨论了 CRISPR-Cas9 介导的基因转换系统在实验室和野生啮齿动物中的使用。尽管在野生释放策略可行之前必须克服技术障碍，但适度的改进可以提高实验室小鼠遗传学的效率并降低成本。以超孟德尔频率遗传的遗传元件可以用于“基因驱动”，将等位基因在人群中传播到高流行率，目的是消除入侵物种或疾病媒介。我们最近证明了 CRISPR-Cas9 介导的基因驱动的基因转换机制在小鼠中是可行的。尽管仍然存在重大技术障碍，但克服这些障碍可能会导致减少啮齿动物传播的莱姆病传播或消除破坏岛屿生态的入侵小鼠和大鼠种群的策略。也许在中等基因转换效率下更容易实现，在实验室环境中的应用可以产生复杂的基因型，与孟德尔遗传策略相比，可以减少金钱和动物生命的时间和成本。在这里，我们讨论了从实现 CRISPR-Cas9 介导的基因转换的早期努力中学到的知识、在实验室中更广泛应用的潜力、当前的局限性以及优化这一潜在强大技术的计划。
This Perspective discusses the use of CRISPR-Cas9-mediated gene conversion systems in laboratory and wild rodents. Although technical hurdles must be overcome before wild-release strategies are feasible, modest improvements could increase the efficiency and reduce the cost of mouse genetics in the laboratory.Genetic elements that are inherited at super-Mendelian frequencies could be used in a 'gene drive' to spread an allele to high prevalence in a population with the goal of eliminating invasive species or disease vectors. We recently demonstrated that the gene conversion mechanism underlying a CRISPR-Cas9-mediated gene drive is feasible in mice. Although substantial technical hurdles remain, overcoming these could lead to strategies that might decrease the spread of rodent-borne Lyme disease or eliminate invasive populations of mice and rats that devastate island ecology. Perhaps more immediately achievable at moderate gene conversion efficiency, applications in a laboratory setting could produce complex genotypes that reduce the time and cost in both dollars and animal lives compared with Mendelian inheritance strategies. Here, we discuss what we have learned from early efforts to achieve CRISPR-Cas9-mediated gene conversion, potential for broader applications in the laboratory, current limitations, and plans for optimizing this potentially powerful technology.