scholarly journals Recent advances in threshold-dependent gene drives for mosquitoes

2018 ◽  
Vol 46 (5) ◽  
pp. 1203-1212 ◽  
Author(s):  
Philip T. Leftwich ◽  
Matthew P. Edgington ◽  
Tim Harvey-Samuel ◽  
Leonela Z. Carabajal Paladino ◽  
Victoria C. Norman ◽  
...  
Keyword(s):  
High Frequency ◽  
Gene Drive ◽  
Fitness Costs ◽  
Practical Applications ◽  
Disease Vector ◽  
Recent Advances ◽  
Mathematical Analyses ◽  
Global Eradication ◽  
Gene Drives

Mosquito-borne diseases, such as malaria, dengue and chikungunya, cause morbidity and mortality around the world. Recent advances in gene drives have produced control methods that could theoretically modify all populations of a disease vector, from a single release, making whole species less able to transmit pathogens. This ability has caused both excitement, at the prospect of global eradication of mosquito-borne diseases, and concern around safeguards. Drive mechanisms that require individuals to be released at high frequency before genes will spread can therefore be desirable as they are potentially localised and reversible. These include underdominance-based strategies and use of the reproductive parasite Wolbachia. Here, we review recent advances in practical applications and mathematical analyses of these threshold-dependent gene drives with a focus on implementation in Aedes aegypti, highlighting their mechanisms and the role of fitness costs on introduction frequencies. Drawing on the parallels between these systems offers useful insights into practical, controlled application of localised drives, and allows us to assess the requirements needed for gene drive reversal.

scholarly journals Invasion and migration of spatially self-limiting gene drives: a comparative analysis

2017 ◽  
Author(s):  
Sumit Dhole ◽  
Michael R. Vella ◽  
Alun L. Loyd ◽  
Fred Gould
Keyword(s):  
Target Population ◽  
Gene Drive ◽  
Fitness Costs ◽  
Invasion And Migration ◽  
Migration Rates ◽  
Chain System ◽  
Drive Systems ◽  
And Migration ◽  
The One ◽  
Gene Drives

AbstractRecent advances in research on gene drives have produced genetic constructs that could theoretically spread a desired gene (payload) into all populations of a species, with a single release in one place. This attribute has advantages, but also comes with risks and ethical concerns. There has been a call for research on gene drive systems that are spatially and/or temporally self-limiting. Here we use a population genetics model to compare the expected characteristics of three spatially self-limiting gene drive systems: one-locus underdominance, two-locus underdominance, and daisy-chain drives. We find large differences between these gene drives in the minimum release size required for successfully driving a payload into a population. The daisy-chain system is the most efficient, requiring the smallest release, followed by the two-locus underdominance system, and then the one-locus underdominance system. However, when the target population exchanges migrants with a non-target population, the gene drives requiring smaller releases suffer from higher risks of unintended spread. For payloads that incur relatively low fitness costs (up to 30%), a simple daisy-chain drive is practically incapable of remaining localized, even with migration rates as low as 0.5% per generation. The two-locus underdominance system can achieve localized spread under a broader range of migration rates and of payload fitness costs, while the one-locus underdominance system largely remains localized. We also find differences in the extent of population alteration and in the permanence of the alteration achieved by the three gene drives. The two-locus underdominance system does not always spread the payload to fixation, even after successful drive, while the daisy-chain system can, for a small set of parameter values, achieve a temporally-limited spread of the payload. These differences could affect the suitability of each gene drive for specific applications.Note:This manuscript has been accepted for publication in the journal Evolutionary Applications and is pending publication. We suggest that any reference to or quotation of this article should be made with this recognition.

scholarly journals Promises and perils of gene drives: Navigating the communication of complex, post-normal science

2019 ◽  
Vol 116 (16) ◽  
pp. 7692-7697 ◽  
Author(s):  
Dominique Brossard ◽  
Pam Belluck ◽  
Fred Gould ◽  
Christopher D. Wirz
Keyword(s):  
Decision Making ◽  
Science Communication ◽  
Social Scientist ◽  
Normal Science ◽  
Gene Drive ◽  
Science Of Science ◽  
Potential Applications ◽  
Technical Assessment ◽  
Gene Drives

In November of 2017, an interdisciplinary panel discussed the complexities of gene drive applications as part of the third Sackler Colloquium on “The Science of Science Communication.” The panel brought together a social scientist, life scientist, and journalist to discuss the issue from each of their unique perspectives. This paper builds on the ideas and conversations from the session to provide a more nuanced discussion about the context surrounding responsible communication and decision-making for cases of post-normal science. Deciding to use gene drives to control and suppress pests will involve more than a technical assessment of the risks involved, and responsible decision-making regarding their use will require concerted efforts from multiple actors. We provide a review of gene drives and their potential applications, as well as the role of journalists in communicating the extent of uncertainties around specific projects. We also discuss the roles of public opinion and online environments in public engagement with scientific processes. We conclude with specific recommendations about how to address current challenges and foster more effective communication and decision-making for complex, post-normal issues, such as gene drives.

scholarly journals Designing gene drives to limit spillover to non-target populations

2019 ◽  
Author(s):  
Gili Greenbaum ◽  
Marcus W. Feldman ◽  
Noah A. Rosenberg ◽  
Jaehee Kim
Keyword(s):  
Target Population ◽  
Unintended Effects ◽  
Gene Drive ◽  
Migration Rates ◽  
Target Populations ◽  
Disease Vector ◽  
Narrow Region ◽  
Natural Settings ◽  
Gene Drives ◽  
High Migration

AbstractThe prospect of utilizing CRISPR-based gene-drive technology for controlling populations, such as invasive and disease-vector species, has generated much excitement. However, the potential for spillovers of gene drive alleles from the target population to non-target populations — events that may be ecologically catastrophic — has raised concerns. Here, using two-population mathematical models, we investigate the possibility of limiting spillovers and impact on non-target populations by designing differential-targeting gene drives, in which the expected equilibrium gene drive allele frequencies are high in the target population but low in the non-target population. We find that achieving differential targeting is possible with certain configurations of gene drive parameters. Most of these configurations ensure differential targeting only under relatively low migration rates between target and non-target populations. Under high migration, differential targeting is possible only in a narrow region of the parameter space. When migration is increased, differential-targeting states can sharply transition to states of global fixation or global loss of the gene drive. Because fixation of the gene drive in the non-target population could severely disrupt ecosystems, we outline possible ways to avoid this outcome. Our results emphasize that, although gene drive technology is promising, understanding the potential consequences for populations other than the targets requires detailed analysis of gene-drive spillovers, and that ways to limit the unintended effects of gene drives to non-target populations should be explored prior to the application of gene drives in natural settings.

scholarly journals A confinable home and rescue gene drive for population modification

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Nikolay P Kandul ◽  
Junru Liu ◽  
Jared B Bennett ◽  
John M Marshall ◽  
Omar S Akbari
Keyword(s):  
Mathematical Modeling ◽  
Target Gene ◽  
Essential Gene ◽  
Gene Drive ◽  
Wild Populations ◽  
Fitness Costs ◽  
Recessive Lethal ◽  
Transmission Rates ◽  
Population Cage ◽  
Gene Drives

Homing based gene drives, engineered using CRISPR/Cas9, have been proposed to spread desirable genes throughout populations. However, invasion of such drives can be hindered by the accumulation of resistant alleles. To limit this obstacle, we engineer a confinable population modification Home-and-Rescue (HomeR) drive in Drosophila targeting an essential gene. In our experiments, resistant alleles that disrupt the target gene function were recessive lethal, and therefore disadvantaged. We demonstrate that HomeR can achieve an increase in frequency in population cage experiments, but that fitness costs due to the Cas9 insertion limit drive efficacy. Finally, we conduct mathematical modeling comparing HomeR to contemporary gene drive architectures for population modification over wide ranges of fitness costs, transmission rates, and release regimens. HomeR could potentially be adapted to other species, as a means for safe, confinable, modification of wild populations.

scholarly journals Role of gene drives in malaria elimination strategy: modeling impact and cost-effectiveness in the Democratic Republic of the Congo

2020 ◽  
Author(s):  
N. Metchanun ◽  
C. Borgemeister ◽  
J. von Braun ◽  
M. Nikolov ◽  
P. Selvaraj ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Malaria Transmission ◽  
Malaria Elimination ◽  
Democratic Republic ◽  
Cost Effective ◽  
Gene Drive ◽  
Republic Of The Congo ◽  
The Impact ◽  
Gene Drives

AbstractThe tremendous burden of malaria has led to renewed efforts on malaria elimination and the development of novel tools for application where existing tools fall short. Gene drive mosquitoes, where transgenes and their associated phenotypes are efficiently propagated to future generations, are under development to suppress vector populations or render vectors incapable of malaria transmission. However, the role of gene drives in an integrated elimination strategy is underexplored. Using a spatially explicit agent-based model of malaria transmission in the Democratic Republic of the Congo, we describe the impact of integrating a population suppression driving-Y gene drive into malaria elimination strategies. We find that as long as the driving-Y construct is extremely effective, releases of gene drive mosquitoes can eliminate malaria, and we identify a cost ceiling for gene drive to be cost-effective relative to existing tools. Vector control via gene drive is worth considering as a supplemental intervention when the construct parameters and costs are suitable.One-sentence summaryWe estimate the impact and cost-effectiveness of gene drive mosquitoes, relative to existing interventions, in malaria elimination strategies

scholarly journals Genetic conversion of a split-drive into a full-drive element

2021 ◽  
Author(s):  
Gerard Terradas ◽  
Jared B. Bennett ◽  
Zhiqian Li ◽  
John M. Marshall ◽  
Ethan Bier
Keyword(s):  
Gene Drive ◽  
Fitness Costs ◽  
Experimental Proof ◽  
Guide Rna ◽  
Split Gene ◽  
Core Components ◽  
Beneficial Traits ◽  
Drive Systems ◽  
Genetic Conversion ◽  
Gene Drives

AbstractGene-drive systems offer an important new avenue for spreading beneficial traits into wild populations. Their core components, Cas9 and guide RNA (gRNA), can either be linked within a single cassette (full gene drive, fGD) or provided in two separate elements (split gene drive, sGD) wherein the gRNA-bearing element drives in the presence of an independent static source of Cas9. We previously designed a system engineered to turn split into full gene drives. Here, we provide experimental proof-of-principle for such a convertible system inserted at the spo11 locus, which is recoded to restore gene function. In multigenerational cage studies, the reconstituted spo11 fGD cassette initially drives with slower kinetics than the unlinked sGD element (using the same Mendelian vasa-Cas9 source), but eventually reaches a similar level of final introgression. Different kinetic behaviors may result from transient fitness costs associated with individuals co-inheriting Cas9 and gRNA transgenes during the drive process.

Calculation-and-experimental estimation of the role of the frequency ratio in changing the endurance at two-frequency deformation modes

2019 ◽  
Vol 85 (1(I)) ◽  
pp. 64-71 ◽  
Author(s):  
M. M. Gadenin
Keyword(s):  
High Frequency ◽  
Experimental Studies ◽  
Low Frequency ◽  
Reduction Factor ◽  
Single Frequency ◽  
Cyclic Loads ◽  
Small Ratio ◽  
Harmonic Components ◽  
Deformation Modes

The cycle configuration at two-frequency loading regimes depends on the number of parameters including the absolute values of the frequencies and amplitudes of the low-frequency and high-frequency loads added during this mode, the ratio of their frequencies and amplitudes, as well as the phase shift between these harmonic components, the latter having a significant effect only with a small ratio of frequencies. Presence of such two-frequency regimes or service loading conditions for parts of machines and structures schematized by them can significantly reduce their endurance. Using the results of experimental studies of changes in the endurance of a two-frequency loading of specimens of cyclically stable, cyclically softened and cyclically hardened steels under rigid conditions we have shown that decrease in the endurance under the aforementioned conditions depends on the ratio of frequencies and amplitudes of operation low-frequency low-cycle and high-frequency vibration stresses, and, moreover, the higher the level of the ratios of amplitudes and frequencies of those stacked harmonic processes of loading the greater the effect. It is shown that estimation of such a decrease in the endurance compared to a single frequency loading equal in the total stress (strains) amplitudes can be carried out using an exponential expression coupling those endurances through a parameter (reduction factor) containing the ratio of frequencies and amplitudes of operation cyclic loads and characteristic of the material. The reduction is illustrated by a set of calculation-experimental curves on the corresponding diagrams for each of the considered types of materials and compared with the experimental data.

Transition metal oxide and chalcogenide-based nanomaterials for antibacterial activities: an overview

Nanoscale ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 6373-6388
Author(s):  
Yanan Tang ◽  
Zhen Qin ◽  
Shengyan Yin ◽  
Hang Sun
Keyword(s):  
Transition Metal ◽  
Metal Oxide ◽  
Transition Metal Oxide ◽  
Antibacterial Activities ◽  
Practical Applications ◽  
Recent Advances

This review summarizes the recent advances of transition metal oxide and chalcogenide-based antibacterial nanomaterials, with emphasis on their inactivation mechanisms and highlighting their practical applications.

Recent advances in the role of Th17/Treg cells in tumor immunity and tumor therapy

2021 ◽  
Author(s):  
Yin Qianmei ◽  
Su Zehong ◽  
Wang Guang ◽  
Li Hui ◽  
Gaojian Lian
Keyword(s):  
Tumor Immunity ◽  
Tumor Therapy ◽  
Treg Cells ◽  
Recent Advances
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