scholarly journals Making gene drive biodegradable

2020 ◽  
Vol 376 (1818) ◽  
pp. 20190804 ◽  
Author(s):  
Josef Zapletal ◽  
Neda Najmitabrizi ◽  
Madhav Erraguntla ◽  
Mark A. Lawley ◽  
Kevin M. Myles ◽  
...  

Gene drive systems have long been sought to modify mosquito populations and thus combat malaria and dengue. Powerful gene drive systems have been developed in laboratory experiments, but may never be used in practice unless they can be shown to be acceptable through rigorous field-based testing. Such testing is complicated by the anticipated difficulty in removing gene drive transgenes from nature. Here, we consider the inclusion of self-elimination mechanisms into the design of homing-based gene drive transgenes. This approach not only caused the excision of the gene drive transgene, but also generates a transgene-free allele resistant to further action by the gene drive. Strikingly, our models suggest that this mechanism, acting at a modest rate (10%) as part of a single-component system, would be sufficient to cause the rapid reversion of even the most robust homing-based gene drive transgenes, without the need for further remediation. Modelling also suggests that unlike gene drive transgenes themselves, self-eliminating transgene approaches are expected to tolerate substantial rates of failure. Thus, self-elimination technology may permit rigorous field-based testing of gene drives by establishing strict time limits on the existence of gene drive transgenes in nature, rendering them essentially biodegradable. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases'.

2020 ◽  
Vol 376 (1818) ◽  
pp. 20190803 ◽  
Author(s):  
Tony Nolan

Gene drives are selfish genetic elements that can be re-designed to invade a population and they hold tremendous potential for the control of mosquitoes that transmit disease. Much progress has been made recently in demonstrating proof of principle for gene drives able to suppress populations of malarial mosquitoes, or to make them refractory to the Plasmodium parasites they transmit. This has been achieved using CRISPR-based gene drives. In this article, I will discuss the relative merits of this type of gene drive, as well as barriers to its technical development and to its deployment in the field as malaria control. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases'.


2021 ◽  
Author(s):  
Xuejiao Xu ◽  
Tim Harvey-Samuel ◽  
Hamid Anees Siddiqui ◽  
Joshua Ang ◽  
Michelle E Anderson ◽  
...  

Promising to provide powerful genetic control tools, gene drives have been constructed in multiple dipterans, yeast and mice, for the purposes of population elimination or modification. However, it remains unclear whether these techniques can be applied to lepidopterans. Here, we used endogenous regulatory elements to drive Cas9 and sgRNA expression in the diamondback moth, (Plutella xylostella), and test the first split-drive system in a lepidopteran. The diamondback moth is an economically important global agriculture pest of cruciferous crops and has developed severe resistance to various insecticides, making it a prime candidate for such novel control strategy development. A very high level of somatic editing was observed in Cas9/sgRNA transheterozygotes, although no significant homing was revealed in the subsequent generation. Although heritable, Cas9-medated germline cleavage, as well as maternal and paternal Cas9 deposition was observed, rates were far lower than for somatic cleavage events, indicating robust somatic but limited germline activity of Cas9/sgRNA under the control of selected regulatory elements. Our results provide valuable experience, paving the way for future construction of gene drive-based genetic control strategies in DBM or other lepidopterans.


2018 ◽  
Vol 175 ◽  
pp. 03058
Author(s):  
Xie Jingwei ◽  
Huang Peng ◽  
Liu Gang

For the reliability modeling of multistate single-component system, single maintenance bench provides the preventive maintenance and alternative maintenance services on the basis of system performance level following the stochastic detection strategy. Phase-type distribution is employed in place of exponential distribution and other typical distributions to describe the stochastic time variable in the reliability modeling process in a unified manner. Through matrix analysis, the analytic expressions for reliability indicators including system steady-state availability, mean time between failures (MTBF) and failure rate of system are obtained. A numerical application is presented to verify the applicability of the model and demonstrate the influence of preventive maintenance threshold and preventive maintenance rate on system reliability.


2012 ◽  
Vol 53 (32) ◽  
pp. 4138-4141 ◽  
Author(s):  
Atsushi Sakai ◽  
Mirai Tanaka ◽  
Eisuke Ohta ◽  
Yuichi Yoshimoto ◽  
Kazuhiko Mizuno ◽  
...  

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