Closing the gap to effective gene drive in Aedes aegypti by exploiting germline regulatory elements.
Closing the gap to effective gene drive in Aedes aegypti by exploiting germline regulatory elements.
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DOI：
10.1038/s41467-023-36029-7
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发表时间：
2023-01-20
影响因子：
16.6
通讯作者：
Alphey, Luke
中科院分区：
文献类型：
--
作者：
Anderson, Michelle A. E.;Gonzalez, Estela;Ang, Joshua X. D.;Shackleford, Lewis;Nevard, Katherine;Verkuijl, Sebald A. N.;Edgington, Matthew P. P.;Harvey-Samuel, Tim;Alphey, Luke
基于CRISPR/Cas9的归巢基因驱动已成为控制蚊子的潜在新方法。虽然已经尝试在埃及伊蚊中开发这样的系统，但是没有一个能够与在按蚊物种中观察到的高驱动效率相匹配。在这里，我们生成Ae。使用种系特异性调控元件测定表达Cas9的埃及伊蚊转基因系，并评估它们偏向sgRNA表达元件（kmosgRNA）遗传的能力。四个shu-Cas9和一个sds 3-Cas9同工酶可以显著地偏置kmosgRNA的遗传，其中sds 3G 1-Cas9分别引起来自携带与野生型异交的两种元件的雄性和雌性的约86%和约94%的最高平均遗传。我们的数学模型表明，sds 3G 1-Cas9可以使kmosgRNA元件的传播达到更高（约15个百分点）的最大载波频率，或者与其他两个已建立的分裂驱动系统相比，更快地实现类似的最大载波频率（12代）。基于CRISPR/Cas9的归巢基因驱动已成为控制蚊子的潜在新方法。在这里，作者使用具有种系特异性调控元件的转基因系来表达Cas9，并实现高达94%的遗传偏倚，缩小了差距.埃及按蚊的高效驱力和按蚊种中观察到的高效驱力。
CRISPR/Cas9-based homing gene drives have emerged as a potential new approach to mosquito control. While attempts have been made to develop such systems in Aedes aegypti, none have been able to match the high drive efficiency observed in Anopheles species. Here we generate Ae. aegypti transgenic lines expressing Cas9 using germline-specific regulatory elements and assess their ability to bias inheritance of an sgRNA-expressing element (kmosgRNAs). Four shu-Cas9 and one sds3-Cas9 isolines can significantly bias the inheritance of kmosgRNAs, with sds3G1-Cas9 causing the highest average inheritance of ~86% and ~94% from males and females carrying both elements outcrossed to wild-type, respectively. Our mathematical model demonstrates that sds3G1-Cas9 could enable the spread of the kmosgRNAs element to either reach a higher (by ~15 percentage point) maximum carrier frequency or to achieve similar maximum carrier frequency faster (by 12 generations) when compared to two other established split drive systems. CRISPR/Cas9-based homing gene drives have emerged as a potential new approach to mosquito control. Here the authors use transgenic lines with germline-specific regulatory elements to express Cas9 and achieve up to 94% inheritance bias, closing the gap between A. aegyptidrives and the highly efficient drives observed in Anopheles species.
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影响因子：
3.7
作者：
Magnusson K;Mendes AM;Windbichler N;Papathanos PA;Nolan T;Dottorini T;Rizzi E;Christophides GK;Crisanti A
通讯作者：
Crisanti A
DOI：
10.1073/pnas.0701515104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Adelman, Zach N.;Jasinskiene, Nijole;James, Anthony A.
通讯作者：
James, Anthony A.
DOI：
10.1073/pnas.1711538114
发表时间：
2017-12-05
影响因子：
11.1
作者：
Li M;Bui M;Yang T;Bowman CS;White BJ;Akbari OS
通讯作者：
Akbari OS
DOI：
10.1073/pnas.1720354115
发表时间：
2018-05-22
影响因子：
11.1
作者：
Champer, Jackson;Liu, Jingxian;Messer, Philipp W.
通讯作者：
Messer, Philipp W.
影响因子：
46.9
作者：
Kyrou K;Hammond AM;Galizi R;Kranjc N;Burt A;Beaghton AK;Nolan T;Crisanti A
通讯作者：
Crisanti A