Tuning CRISPR-Cas9 Gene Drives in Saccharomyces cerevisiae.
Tuning CRISPR-Cas9 Gene Drives in Saccharomyces cerevisiae.
复制标题
DOI：
10.1534/g3.117.300557
复制
发表时间：
2018-03-02
期刊：
影响因子：
--
通讯作者：
Finnigan GC
中科院分区：
文献类型：
--
作者：
Roggenkamp E;Giersch RM;Schrock MN;Turnquist E;Halloran M;Finnigan GC
控制生物种群是许多领域的持续挑战，包括农业、生物多样性、生态保护、害虫控制和疾病传播。在某些情况下，例如携带人类病原体的昆虫（例如，疟疾），消灭或减少少数物种将对整个地球仪产生巨大影响。鉴于CRISPR-Cas9基因编辑技术的最新发现和发展，该系统的独特安排，即基于核酸酶的“基因驱动”，允许遗传元件在种群中的超级孟德尔传播和强制繁殖。最近的研究表明，基因驱动能够在实验室环境中迅速传播并几乎消灭昆虫种群。虽然设计用于野生种群的更优化的基因驱动仍然存在技术挑战，但围绕这种强大的生物制剂的性质仍然存在严重的生态和伦理问题。在这里，我们使用芽殖酵母作为一个安全和完全包含的模型系统来探索可能允许基因驱动活性的程序化调节的机制。我们描述了所有基于CRISPR的驱动器的四个保守特征，并证明了每个驱动器组件-Cas9蛋白水平，sgRNA身份，Cas9核质穿梭和新型Cas9-Cas9串联融合-调节群体内驱动器活性的能力。
Control of biological populations is an ongoing challenge in many fields, including agriculture, biodiversity, ecological preservation, pest control, and the spread of disease. In some cases, such as insects that harbor human pathogens (e.g., malaria), elimination or reduction of a small number of species would have a dramatic impact across the globe. Given the recent discovery and development of the CRISPR-Cas9 gene editing technology, a unique arrangement of this system, a nuclease-based “gene drive,” allows for the super-Mendelian spread and forced propagation of a genetic element through a population. Recent studies have demonstrated the ability of a gene drive to rapidly spread within and nearly eliminate insect populations in a laboratory setting. While there are still ongoing technical challenges to design of a more optimal gene drive to be used in wild populations, there are still serious ecological and ethical concerns surrounding the nature of this powerful biological agent. Here, we use budding yeast as a safe and fully contained model system to explore mechanisms that might allow for programmed regulation of gene drive activity. We describe four conserved features of all CRISPR-based drives and demonstrate the ability of each drive component—Cas9 protein level, sgRNA identity, Cas9 nucleocytoplasmic shuttling, and novel Cas9-Cas9 tandem fusions—to modulate drive activity within a population.
登录
查看更多内容
影响因子：
12.3
作者：
Dang Y;Jia G;Choi J;Ma H;Anaya E;Ye C;Shankar P;Wu H
通讯作者：
Wu H
影响因子：
46.9
作者：
Doench JG;Fusi N;Sullender M;Hegde M;Vaimberg EW;Donovan KF;Smith I;Tothova Z;Wilen C;Orchard R;Virgin HW;Listgarten J;Root DE
通讯作者：
Root DE
DOI：
10.1016/bs.pmbts.2017.03.011
发表时间：
2017
影响因子：
--
作者：
Baltes NJ;Gil-Humanes J;Voytas DF
通讯作者：
Voytas DF
影响因子：
16
作者：
Briner, Alexandra E.;Donohoue, Paul D.;Barrangou, Rodolphe
通讯作者：
Barrangou, Rodolphe
影响因子：
3
作者：
Beaghton, Andrea;Beaghton, Pantelis John;Burt, Austin
通讯作者：
Burt, Austin