The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives.
The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives.
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DOI：
10.3389/fbioe.2022.856981
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发表时间：
2022
影响因子：
5.7
通讯作者：
Anderson MAE
中科院分区：
文献类型：
--
作者：
Verkuijl SAN;Ang JXD;Alphey L;Bonsall MB;Anderson MAE
对野生种群进行离散和精确的遗传改变已被提议作为解决昆虫害虫造成的一些世界上最紧迫的生态和公共卫生挑战的一种手段。能够实现这一点的技术，如合成基因驱动，已经开发了几十年。最近，新一代可编程核酸酶极大地加速了技术发展。CRISPR-Cas9提高了基因工程的效率，并已被用作不同基因驱动遗传偏置机制中的主要效应核酸酶。在这些基于核酸酶的基因驱动器中，归巢核酸内切酶基因驱动器已经成为大量研究工作的主题（特别是在昆虫中），在类似的核心设计上已经开发了许多不同的迭代。我们绘制了归巢基因驱动发展的历史，突出了出现的挑战，如意外的修复结果，“泄漏”的表达，和父母的沉积。最后，我们讨论了在开发策略以提高归巢核酸内切酶基因驱动的效率并减轻或防止意外结果方面取得的进展。
Making discrete and precise genetic changes to wild populations has been proposed as a means of addressing some of the world’s most pressing ecological and public health challenges caused by insect pests. Technologies that would allow this, such as synthetic gene drives, have been under development for many decades. Recently, a new generation of programmable nucleases has dramatically accelerated technological development. CRISPR-Cas9 has improved the efficiency of genetic engineering and has been used as the principal effector nuclease in different gene drive inheritance biasing mechanisms. Of these nuclease-based gene drives, homing endonuclease gene drives have been the subject of the bulk of research efforts (particularly in insects), with many different iterations having been developed upon similar core designs. We chart the history of homing gene drive development, highlighting the emergence of challenges such as unintended repair outcomes, “leaky” expression, and parental deposition. We conclude by discussing the progress made in developing strategies to increase the efficiency of homing endonuclease gene drives and mitigate or prevent unintended outcomes.
影响因子：
4.4
作者：
Sutton ER;Yu Y;Shimeld SM;White-Cooper H;Alphey AL
通讯作者：
Alphey AL