BACKGROUND The discovery of CRISPR-based gene editing and its application to homing-based gene drive systems has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. Gene drive systems that display threshold-dependent behavior could potentially be used during the trial phase of this technology, or when localized control is otherwise desired, as simple models predict them to spread into partially isolated populations in a confineable manner, and to be reversible through releases of wild-type organisms. Here, we model hypothetical releases of two recently engineered threshold-dependent gene drive systems-reciprocal chromosomal translocations and a form of toxin-antidote-based underdominance known as UDMEL-to explore their ability to be confined and remediated. RESULTS We simulate releases of Aedes aegypti, the mosquito vector of dengue, Zika, and other arboviruses, in Yorkeys Knob, a suburb of Cairns, Australia, where previous biological control interventions have been undertaken on this species. We monitor spread to the neighboring suburb of Trinity Park to assess confinement. Results suggest that translocations could be introduced on a suburban scale, and remediated through releases of non-disease-transmitting male mosquitoes with release sizes on the scale of what has been previously implemented. UDMEL requires fewer releases to introduce, but more releases to remediate, including of females capable of disease transmission. Both systems are expected to be confineable to the release site; however, spillover of translocations into neighboring populations is less likely. CONCLUSIONS Our analysis supports the use of translocations as a threshold-dependent drive system capable of spreading disease-refractory genes into Ae. aegypti populations in a confineable and reversible manner. It also highlights increased release requirements when incorporating life history and population structure into models. As the technology nears implementation, further ecological work will be essential to enhance model predictions in preparation for field trials.

中文翻译：

---

在空间明确的埃及伊蚊种群中模拟阈值依赖性基因驱动系统的限制和可逆性。

背景技术基于CRISPR的基因编辑的发现及其在基于归巢的基因驱动系统中的应用引起了人们的兴奋，因为它具有广泛控制蚊媒疾病的潜力，并引起了人们对CRISPR的侵袭性和潜在不可逆性的担忧。释放。显示阈值依赖性行为的基因驱动系统可能会在该技术的试验阶段使用，或者在需要局部控制的情况下使用，因为简单的模型预测它们会以可限制的方式扩散到部分孤立的种群中，并通过以下方式可逆释放野生型生物。这里，我们对两个最近工程化的阈值依赖性基因驱动系统（相互的染色体易位）和一种基于毒素-解毒剂的显着性（称为UDMEL）形式的假设释放进行建模，以探索其被限制和修复的能力。结果我们模拟了埃及凯恩斯郊区约克西诺布的埃及伊蚊，登革热，寨卡病毒和其他虫媒病毒的灭蚊载体的释放，此前该生物已经在对该物种进行了生物防治措施。我们会监测到邻近地区三位一体公园的蔓延情况，以评估禁闭情况。结果表明，可以在郊区范围内引入易位，并通过释放非疾病传播的雄性蚊子进行补救，释放的规模与先前实施的规模相同。UDMEL要求引入的发行版更少，但有更多的释放需要补救，包括能够传播疾病的雌性。预计这两个系统都限于发布站点；但是，易位向周边人口溢出的可能性较小。结论我们的分析支持易位作为阈值依赖性驱动系统的使用，能够将疾病难治性基因传播到Ae中。埃及种群数量有限且可逆。它还强调了将生活史和人口结构纳入模型时对释放的要求增加。随着该技术即将实施，进一步的生态工作对于增强模型预测以进行现场试验至关重要。然而，易位向周边人口溢出的可能性较小。结论我们的分析支持易位作为阈值依赖性驱动系统的使用，能够将疾病难治性基因传播到Ae中。埃及种群数量有限且可逆。它还强调了将生活史和人口结构纳入模型时对释放的要求增加。随着该技术即将实施，进一步的生态工作对于增强模型预测以进行现场试验至关重要。然而，易位向周边人口溢出的可能性较小。结论我们的分析支持易位作为阈值依赖性驱动系统的使用，能够将疾病难治性基因传播到Ae中。埃及种群数量有限且可逆。它还强调了将生活史和人口结构纳入模型时对释放的要求增加。随着该技术即将实施，进一步的生态工作对于增强模型预测以进行现场试验至关重要。它还强调了将生活史和人口结构纳入模型时对释放的要求增加。随着该技术即将实施，进一步的生态工作对于增强模型预测以进行现场试验至关重要。它还强调了将生活史和人口结构纳入模型时对释放的要求增加。随着该技术即将实施，进一步的生态工作对于增强模型预测以进行现场试验至关重要。