Division of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA, USA.
Nat Protoc. 2022 Jan;17(1):3-14. doi: 10.1038/s41596-021-00646-7. Epub 2021 Dec 23.
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.
以超孟德尔频率遗传的遗传元件可用于“基因驱动”，将一个等位基因传播到高流行率的种群中，以消除入侵物种或疾病媒介。我们最近证明，CRISPR-Cas9 介导的基因驱动背后的基因转换机制在小鼠中是可行的。尽管仍然存在大量技术障碍，但克服这些障碍可能会导致一些策略的出现，这些策略可能会减少啮齿动物传播的莱姆病的传播，或者消除破坏岛屿生态的入侵性老鼠和大鼠种群。在中等基因转换效率下，也许更能立即实现的应用是在实验室环境中产生复杂的基因型，与孟德尔遗传策略相比，这可以减少时间和成本，无论是在金钱还是动物生命方面。在这里，我们讨论了从早期实现 CRISPR-Cas9 介导的基因转换的努力中吸取的经验教训、在实验室中更广泛应用的潜力、当前的限制以及优化这一潜在强大技术的计划。
