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Articles by Jackson Champer
Finding the perfect promoter for Cas9 in homing gene drives using single cell transcriptome data
Abstract Gene drive can modify or suppress vector populations by spreading drive alleles. In CRISPR homing drives, regulating Cas9 expression has been effective for improving drive performance, but selecting suitable promoters is often a major challenge. Here, we evaluate 35 Cas9 constructs with distinct promoters in Drosophila melanogaster and identify associations between drive performance and single-cell RNA expression patterns of the promoter-associated genes.
Self-limiting population suppression gene drive design in the West Nile vector mosquito, Culex quinquefasciatus
Abstract Culex quinquefasciatus is a major vector of West Nile virus and other pathogens, yet genetic population suppression tools for this species remain limited. Here, we develop a self-limiting, CRISPR-based suppression gene drive system targeting doublesex, close to the male-determining locus, promoting male transmission. A recoded dsxM sequence converts females into sterile intersexes, preventing population-level spread.
Abstract CRISPR homing drives can be used to suppress a population by targeting female fertility genes. They convert wild-type alleles to drive alleles in the germline of drive heterozygotes, but resistance alleles can weaken suppressive power, or even stop suppression if they preserve the function of the target gene. We use multiplexed gRNAs targeting doublesex in Drosophila to avoid functional resistance and create resistance alleles that were dominant female-sterile.
Seed dormancy shapes gene drive dynamics in plants
Abstract Gene drives offer revolutionary potential for the management of problematic plant populations, such as invasive weeds and herbicide-resistant species, by rapidly spreading desired genetic alterations. Two recent studies have provided experimental demonstrations of engineered CRISPR gene drive systems in plants (CAIN and ClvR).
A systematic delineation of 3′UTR regulatory elements and their contextual associations
Abstract The 3′ region of genes plays a crucial role in transcriptional and post-transcriptional regulation, yet the functional elements within it remain largely unknown. Here, we assessed the impact of over 1.6 million synthetic 3′UTR sequences on transcript abundance and subcellular localization in A549 cells, revealing a substantial number of relatively independent elements with distinct regulatory associations.
Investigating multiple types of resistance against a homing gene drive in European populations of Drosophila melanogaster
Abstract Gene drive technology may be a valuable tool for addressing several contemporary challenges, including combating disease vectors, conserving biodiversity, and controlling agricultural pests. Homing gene drives spread through a population by copying themselves onto the homologous chromosome in the germline of heterozygous individuals.
A simulation-based deep learning framework for spatially explicit malaria modeling of CRISPR suppression gene drive mosquitoes
Abstract Engineered CRISPR gene drives are a promising new strategy for fighting malaria and other vector-borne diseases, made possible by genome engineering with the CRISPR-Cas9 system. One useful approach to predict the outcome of a gene drive mosquito release is individual-based modeling, which can be spatially explicit and allows flexible parameters for drive efficiency, mosquito ecology, and malaria transmission.
Modeling control of invasive fire ants by gene drive
Abstract Solenopsis invicta, commonly known as the fire ant, is characterized by aggressive behavior and exceptional invasive capabilities, rendering conventional control methods largely ineffective. Here, we explore the implementation of homing suppression gene drive in fire ants by developing a spatially explicit model that incorporates both monogyne and polygyne colony structures, enabling comprehensive evaluation of genetic control strategies.
Resource‐explicit interactions in spatial population models
1 INTRODUCTION In this study, we introduce a novel modelling technique for individual-based simulations of continuous-space populations in which competition between individuals is mediated by abstractly simulated resources within the modelled area.
A comparative assessment of self-limiting genetic control strategies for population suppression
Abstract Genetic control strategies are promising solutions for control of pest populations and invasive species. Methods utilizing repeated releases of males such as Sterile Insect Technique (SIT), Release of Insects carrying a Dominant Lethal (RIDL), self-limiting gene drives, and gene disruptors are highly controllable methods, ensuring biosafety. Although models of these strategies have been built, detailed comparisons are lacking, particularly for some of the newer strategies.
Deployment of tethered gene drive for confined suppression in continuous space requires avoiding drive wave interference
ACKNOWLEDGEMENTS The cluster-based data collection was assisted by High-Performance Computing Platform of the Center for Life Science at Peking University. Supporting Information Filename Description mec17530-sup-0001-Supinfo.pdfPDF document, 10.5 MB Data S1. REFERENCES , , , , , , , , , , , , & (2020). Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi. Nature Communications, 11, 1–13. (2014). Genetic control of mosquitoes.
Deployment of tethered gene drive for confined suppression in continuous space requires avoiding drive wave interference
Abstract Gene drives have great potential for suppression of pest populations and removal of exotic invasive species. CRISPR homing suppression drive is a powerful but unconfined drive, posing risks of uncontrolled spread. Thus, developing methods for confining a gene drive is of great significance. Tethered drive combines a confined system such as Toxin-Antidote Recessive Embryo (TARE) drive with a strong drive such as a homing suppression drive.
Overriding Mendelian inheritance in Arabidopsis with a CRISPR toxin–antidote gene drive that impairs pollen germination - Nature Plants
Abstract Synthetic gene drives, inspired by natural selfish genetic elements and transmitted to progeny at super-Mendelian (>50%) frequencies, present transformative potential for disseminating traits that benefit humans throughout wild populations, even facing potential fitness costs. Here we constructed a gene drive system in plants called CRISPR-Assisted Inheritance utilizing NPG1 (CAIN), which uses a toxin–antidote mechanism in the male germline to override Mendelian inheritance.
Resource-explicit interactions in spatial population models
Abstract Continuous-space population models can yield significantly different results from their panmictic counterparts when assessing evolutionary, ecological, or population-genetic processes. However, the computational burden of spatial models is typically much greater than that of panmictic models due to the overhead of determining which individuals interact with one another and how strongly they interact.
Overriding Mendelian inheritance in Arabidopsis with a CRISPR toxin-antidote gene drive that impairs pollen germination
Abstract Synthetic gene drives, inspired by natural selfish genetic elements, present transformative potential for disseminating traits that benefit humans throughout wild populations, irrespective of potential fitness costs. Here, we constructed a gene drive system called CRISPR-Assisted Inheritance utilizing NPG1 (CAIN), which employs a toxin-antidote mechanism in the male germline to override Mendelian inheritance in plants.
Making waves: Comparative analysis of gene drive spread characteristics in a continuous space model
Supporting Information Filename Description mec17131-sup-0001-AppendixS1.pdfPDF document, 1.5 MB Appendix S1 REFERENCES , , , , , & (2021). Wolbachia cifB induces cytoplasmic incompatibility in the malaria mosquito vector. Nature Microbiology, 6(12), 1575–1582. https://doi.org/10.1038/s41564-021-00998-6 , , , , , , , , , , , , & (2020). Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi. Nature Communications, 11(1), 1–13.
Population suppression by release of insects carrying a dominant sterile homing gene drive targeting doublesex in Drosophila
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Modeling emergence of Wolbachia toxin-antidote protein functions with an evolutionary algorithm
Introduction TA systems typically involve two linked genes encoding a toxin and antidote (Yamaguchi et al., 2011). They skew Mendelian inheritance in their favor by addicting organisms to the presence of an antidote and killing offspring that do not inherit the TA module, via the toxin. Thus, they ensure inheritance in the next generation by post segregational killing.
Adversarial interspecies relationships facilitate population suppression by gene drive in spatially explicit models
Abstract Suppression gene drives bias their inheritance to spread through a population, potentially eliminating it when they reach high frequency. CRISPR homing suppression drives have already seen success in the laboratory, but several models predict that success may be elusive in population with realistic spatial structure due to extinction-recolonization cycles. Here, we extend our continuous space framework to include two competing species or predator–prey pairs.
Assessment of distant-site rescue elements for CRISPR toxin-antidote gene drives
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Making waves: Comparative analysis of gene drive spread characteristics in a continuous space model
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Symbionts and gene drive: two strategies to combat vector-borne disease
Highlights Safe and sustainable approaches for mosquito control are critical due to the global increasing burden of mosquito-transmitted diseases. Novel control approaches based on symbionts are currently proposed to modify or suppress mosquito populations and Wolbachia-based methods have already achieved some success in field trials. Transgenic mosquitoes carrying gene drives that spread through populations are a promising control approach to block disease transmission or suppress vector species.
A CRISPR homing gene drive targeting a haplolethal gene removes resistance alleles and successfully spreads through a cage population
Along with bragging rights, the nations that achieve exascale computing early will have a leg up in the scientific revolutions of the future.
CRISPR gene drives could eliminate many vector-driven pests and diseases, but challenges remain
The GLP Needs Your Help It is easier than ever for advocacy groups to spread disinformation on pressing science issues, such as the ongoing coronavirus pandemic. No, vaccines are not harmful. Yes, the use of biotechnology, GMOs or gene editing to develop antigens for treatments including vaccines are part of the solution. To inform the public about what’s really going on, we present the facts and challenge those who don't. We can’t do this work without your help.
Performance analysis of novel toxin-antidote CRISPR gene drive systems
Abstract Background CRISPR gene drive systems allow the rapid spread of a genetic construct throughout a population. Such systems promise novel strategies for the management of vector-borne diseases and invasive species by suppressing a target population or modifying it with a desired trait. However, current homing-type drives have two potential shortcomings. First, they can be thwarted by the rapid evolution of resistance.
Improved CRISPR gene drive solves problems of old tech
Gene drives use genetic engineering to create a desired mutation in a few individuals that then spreads via mating throughout a population in fewer than 10 generations. A CRISPR gene drive that carries a red fluorescent protein as payload is spread through a population of fruit flies in laboratory experiments. In theory, such a mechanism could be used to prevent malarial mosquitoes from transmitting disease, or possibly to wipe out an invasive species by disabling its ability to reproduce.
A toxin-antidote CRISPR gene drive system for regional population modification
Abstract Engineered gene drives based on a homing mechanism could rapidly spread genetic alterations through a population. However, such drives face a major obstacle in the form of resistance against the drive. In addition, they are expected to be highly invasive. Here, we introduce the Toxin-Antidote Recessive Embryo (TARE) drive. It functions by disrupting a target gene, forming recessive lethal alleles, while rescuing drive-carrying individuals with a recoded version of the target.
Maximum likelihood estimation of fitness components in experimental evolution
Maximum likelihood estimation of fitness components in experimental evolution Jingxian Liu, Jackson Champer, Chen Liu, Joan Chung, Riona Reeves, Anisha Luthra, Yoo Lim Lee, Andrew G Clark, Philipp W Messer bioRxiv 345660; doi: https://doi.org/10.1101/345660
Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations
A functioning gene drive system could fundamentally change our strategies for the control of vector-borne diseases by facilitating rapid dissemination of transgenes that prevent pathogen transmission or reduce vector capacity. CRISPR/Cas9 gene drive promises such a mechanism, which works by converting cells that are heterozygous for the drive construct into homozygotes, thereby enabling super-Mendelian inheritance.
The role of the vaginal microbiome in gynecological cancer: a review
Human microbiome research has shown commensal bacteria to be a major factor in both wellness and disease pathogenesis. Interest in the microbiome has recently expanded beyond the gut to include a multitude of other organ systems for which the microbiome may have health implications. Here, we review the role of the vaginal microbiome in health and disease, with a particular focus on gynecologic malignancies.
Novel CRISPR/Cas9 gene drive constructs in Drosophila reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations | bioRxiv
Novel CRISPR/Cas9 gene drive constructs in Drosophila reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations Jackson Champer, Riona Reeves, Suh Yeon Oh, Chen Liu, Jingxian Liu, Andrew G Clark, Philipp W Messer bioRxiv 112011; doi: https://doi.org/10.1101/112011
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