Design and analysis of CRISPR-based underdominance toxin-antidote gene drives.
Design and analysis of CRISPR-based underdominance toxin-antidote gene drives.
复制标题
DOI：
10.1111/eva.13180
复制
发表时间：
2021-04
影响因子：
4.1
通讯作者：
Messer PW
中科院分区：
文献类型：
--
作者：
Champer J;Champer SE;Kim IK;Clark AG;Messer PW
CRISPR基因驱动系统提供了一种在整个群体中传递所需转基因的机制，用于从媒介传播疾病控制到入侵物种抑制的目的。在这项模拟研究中，我们评估了几种基于CRISPR的欠显性基因驱动构建体的性能，这些构建体采用了毒素解毒剂（TA）原则。这些驱动器使用CRISPR核酸酶（毒素）破坏必需基因的野生型版本，同时携带基因的重新编码版本（解毒剂）。这种性质的驱动器允许可能被限制在所需地理位置的释放。这是因为这种驱动器具有驱动器在人群中传播所需的非零入侵阈值频率。我们模型驱动器的目标是单倍或单倍致死的必需基因，使用核酸酶启动子与限制生殖系的表达，启动子，另外导致在早期胚胎从母体沉积的切割活性，和启动子，具有普遍存在的体细胞表达。我们还研究了几种可能的驱动器架构，考虑了“同站点”和“远站点”系统，以及几种面向磁盘的驱动器。总之，这些驱动变体为群体修饰和抑制提供了广泛的入侵阈值频率和选择。我们的研究结果表明，CRISPR TA欠显性驱动系统可以允许设计灵活且可能受限的基因驱动策略。
CRISPR gene drive systems offer a mechanism for transmitting a desirable transgene throughout a population for purposes ranging from vector‐borne disease control to invasive species suppression. In this simulation study, we assess the performance of several CRISPR‐based underdominance gene drive constructs employing toxin‐antidote (TA) principles. These drives disrupt the wild‐type version of an essential gene using a CRISPR nuclease (the toxin) while simultaneously carrying a recoded version of the gene (the antidote). Drives of this nature allow for releases that could be potentially confined to a desired geographic location. This is because such drives have a nonzero‐invasion threshold frequency required for the drive to spread through the population. We model drives which target essential genes that are either haplosufficient or haplolethal, using nuclease promoters with expression restricted to the germline, promoters that additionally result in cleavage activity in the early embryo from maternal deposition, and promoters that have ubiquitous somatic expression. We also study several possible drive architectures, considering both “same‐site” and “distant‐site” systems, as well as several reciprocally targeting drives. Together, these drive variants provide a wide range of invasion threshold frequencies and options for both population modification and suppression. Our results suggest that CRISPR TA underdominance drive systems could allow for the design of flexible and potentially confinable gene drive strategies.
登录
查看更多内容
影响因子：
4.6
作者：
Eritja R;Palmer JRB;Roiz D;Sanpera-Calbet I;Bartumeus F
通讯作者：
Bartumeus F
影响因子：
2
作者：
Davis, S;Bax, N;Grewe, P
通讯作者：
Grewe, P
影响因子：
56.9
作者：
Chen, Chun-Hong;Huang, Haixia;Hay, Bruce A.
通讯作者：
Hay, Bruce A.
影响因子：
3.3
作者：
Champer, Jackson;Wen, Zhaoxin;Clark, Andrew G.
通讯作者：
Clark, Andrew G.
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.