Containment strategies for synthetic gene drive organisms and impacts on gene flow.

2021 ◽  
pp. 137-152
Author(s):  
Lei Pei ◽  
Markus Schmidt
Keyword(s):  
Gene Flow ◽  
Fungal Infections ◽  
Basic Research ◽  
Fruit Fly ◽  
Mitigation Strategies ◽  
Synthetic Gene ◽  
Model Organisms ◽  
Gene Drive ◽  
Comprehensive Overview ◽  
Gene Drives

Abstract Gene drives, particularly synthetic gene drives, may help to address some important challenges, by efficiently altering specific sections of DNA in entire populations of wild organisms. Here we review the current development of the synthetic gene drives, especially those RNA-guided synthetic gene drives based on the CRISPR nuclease Cas. Particular focuses are on their possible applications in agriculture (e.g. disease resistance, weed control management), ecosystem conservation (e.g. evasion species control), health (e.g. to combat insect-borne and fungal infections), and for basic research in model organisms (e.g. Saccharomyces, fruit fly, and zebra fish). The physical, chemical, biological, and ecological containment strategies that might help to confine these gene drive-modified organisms are then explored. The gene flow issues, those from gene drive-derived organisms to the environment, are discussed, while possible mitigation strategies for gene drive research are explored. Last but not least, the regulatory context and opinions from key stakeholders (regulators, scientists, and concerned organizations) are reviewed, aiming to provide a more comprehensive overview of the field.

CRISPR-Clear: A Fieldable Detection Procedure for Potential CRISPR-Cas9 Gene Drive Based Bioweapons

2019 ◽  
Author(s):  
Anna C. Nieuwenweg ◽  
Martijn M. van Galen ◽  
Angelina Horsting ◽  
Jorrit W. Hegge ◽  
Aldrik Velders ◽  
...  
Keyword(s):  
Genetic Modification ◽  
Screening Method ◽  
Dna Amplification ◽  
Synthetic Gene ◽  
Rapid Progression ◽  
Gene Drive ◽  
Naked Eye ◽  
Amplification Technique ◽  
Specific Alteration ◽  
Gene Drives

<p>Rapid progression in genetic modification research has made gene editing increasingly cheaper and easier to use. CRISPR-Cas9 for example, allows for the specific alteration of the genome of an organism with relative simplicity and low costs. This raised a worrying question; can genetic modification techniques be used to create novel bioweapons? A specific scenario is the initiation of a synthetic gene drive for malicious purposes. A synthetic gene drive can be used to quickly spread a mutation through an entire population. This mutation could alter vectors in such a way that they will spread human diseases or eradicate essential organisms. Since a gene drive spreads efficiently through a population, timely detection is essential. Thus, a quick and field deployable screening method is needed to counteract the malicious use of gene drives. </p> <p>Here, we show a battery-operated, sensitive screening method, named CRISPR-Clear, for the detection of gene drive modified organisms. CRISPR-Clear is based on the combination of three components: 1) A DNA amplification technique known as loop-mediated isothermal amplification (LAMP) for detecting the presence of a gene drive; b) a portable battery-operated Arduino device which heats up the sample to allow DNA amplification, and c) a naked-eye visualization of the results. </p> <p>We designed and tested six LAMP primers targeting a Cas9 endonuclease-based gene drive, assembled a battery-operated Arduino device and tested the naked-eye visualization method. In addition, we were able to detect the presence of the Cas9 gene, extracted from a transformed bacteria, providing a proof-of-concept of the CRISPR-Clear device.</p>

scholarly journals The value of interdisciplinary research: lessons from the 2017 Nobel Prize in chronobiology

2018 ◽  
Vol 12 (1) ◽  
pp. 25-28
Author(s):  
Jadwiga M. Giebultowicz
Keyword(s):  
Nobel Prize ◽  
Molecular Mechanisms ◽  
Biological Clock ◽  
Basic Research ◽  
Fruit Fly ◽  
Short Review ◽  
Model Organisms ◽  
Biological Clocks ◽  
Daily Rhythms ◽  
Interdisciplinary Work

Since 1901, the Nobel Prize has been awarded to scientists who have made the most important discoveries for the benefit of humanity. The 2017 Nobel Prize in Physiology or Medicine was awarded jointly to Jeffrey C. Hall, Michael Rosbash and Michael W. Young “for their discoveries of molecular mechanisms controlling the circadian rhythm.” It may be surprising to learn that those three scientists dedicated their entire careers to research on the fruit fly, Drosophila melanogaster. However, as their studies progressed, it became increasingly clear that the mechanism of the biological clock that they discovered in Drosophila is very similar to a timekeeping mechanism present in mammals, including humans. Through interdisciplinary work between scientists performing basic research on model organisms and doctors working in medical schools, we have learned over time that daily rhythms support human health while disruption of these rhythms is associated with a range of pathological disorders such as cardiovascular problems, metabolic, neurological, and many other diseases. This short review will highlight critical milestones on the way to understanding biological clocks, focusing on the roles played by the three Nobel Prize winners.

scholarly journals CRISPR with independent transgenes is a safe and robust alternative to autonomous gene drives in basic research

2015 ◽  
Author(s):  
Fillip Port ◽  
Nadine Muschalik ◽  
Simon L Bullock
Keyword(s):  
Gene Editing ◽  
Genome Engineering ◽  
High Efficiency ◽  
Basic Research ◽  
Evidence Based ◽  
Gene Drive ◽  
Highly Active ◽  
Genome Modification ◽  
Target Sites ◽  
Gene Drives

CRISPR/Cas technology allows rapid, site-specific genome modification in a wide variety of organisms. CRISPR components produced by integrated transgenes have been shown to mutagenise some genomic target sites in Drosophila melanogaster with high efficiency, but whether this is a general feature of this system remains unknown. Here, we systematically evaluate available CRISPR/Cas reagents and experimental designs in Drosophila. Our findings allow evidence-based choices of Cas9 sources and strategies for generating knock-in alleles. We perform gene editing at a large number of target sites using a highly active Cas9 line and a collection of transgenic gRNA strains. The vast majority of target sites can be mutated with remarkable efficiency using these tools. We contrast our method to recently developed autonomous gene drive technology for genome engineering (Gantz & Bier, 2015) and conclude that optimised CRISPR with independent transgenes is as efficient, more versatile and does not represent a biosafety risk.

scholarly journals Drosophila Short stop as a paradigm for the role and regulation of spectraplakins

2017 ◽  
Author(s):  
Andre Voelzmann ◽  
Yu-Ting Liew ◽  
Yue Qu ◽  
Ines Hahn ◽  
Cristina Melero ◽  
...  
Keyword(s):  
Genetic Model ◽  
Current Knowledge ◽  
Fruit Fly ◽  
Model Organisms ◽  
Functional Domains ◽  
Cellular Functions ◽  
Comprehensive Overview ◽  
Characteristic Functional ◽  
Intracellular Organelles ◽  
Linker Molecules

AbstractSpectraplakins are evolutionarily well conserved cytoskeletal linker molecules that are true members of three protein families: plakins, spectrins and Gas2-like proteins. Spectraplakin genes encode at least 7 characteristic functional domains which are combined in a modular fashion into multiple isoforms, and which are responsible for an enormous breadth of cellular functions. These functions are related to the regulation of actin, microtubules, intermediate filaments, intracellular organelles, cell adhesions and signalling processes during the development and maintenance of a wide variety of tissues. To gain a deeper understanding of this enormous functional diversity, invertebrate genetic model organisms, such as the fruit fly Drosophila, can be used to develop concepts and mechanistic paradigms that can inform the investigation in higher animals or humans. Here we provide a comprehensive overview of our current knowledge of the Drosophila spectraplakin Short stop (Shot). We describe its functional domains and isoforms and compare them with those of the mammalian spectraplakins dystonin and MACF1. We then summarise its roles during the development and maintenance of the nervous system, epithelia, oocytes and muscles, taking care to compare and contrast mechanistic insights across these functions in the fly, but especially also with related functions of dystonin and MACF1 in mostly mammalian contexts. We hope that this review will improve the wider appreciation of how work on Drosophila Shot can be used as an efficient strategy to promote the fundamental concepts and mechanisms that underpin spectraplakin functions, with important implications for biomedical research into human disease.

scholarly journals Development of a multi-locus CRISPR gene drive system in budding yeast

2018 ◽  
Author(s):  
Yao Yan ◽  
Gregory C. Finnigan
Keyword(s):  
Budding Yeast ◽  
Basic Research ◽  
Single Copy ◽  
Drive System ◽  
Gene Drive ◽  
Agricultural Pests ◽  
Guide Rnas ◽  
And Control ◽  
Gene Drives ◽  
Control Inhibition

ABSTRACTThe discovery of CRISPR/Cas gene editing has allowed for major advances in many biomedical disciplines and basic research. One arrangement of this biotechnology, a nuclease-based gene drive, can rapidly deliver a genetic element through a given population and studies in fungi and metazoans have demonstrated the success of such a system. This methodology has the potential to control biological populations and contribute to eradication of insect-borne diseases, agricultural pests, and invasive species. However, there remain challenges in the design, optimization, and implementation of gene drives including concerns regarding biosafety, containment, and control/inhibition. Given the numerous gene drive arrangements possible, there is a growing need for more advanced designs. In this study, we use budding yeast to develop an artificial multi-locus gene drive system. Our minimal setup requires only a single copy of S. pyogenes Cas9 and three guide RNAs to propagate three separate gene drives. We demonstrate how this system could be used for targeted allele replacement of native genes and to suppress NHEJ repair systems by modifying DNA Ligase IV. A multi-locus gene drive configuration provides an expanded suite of options for complex attributes including pathway redundancy, combatting evolved resistance, and safeguards for control, inhibition, or reversal of drive action.

scholarly journals Engineered Reproductively Isolated Species Drive Reversible Population Replacement

2020 ◽  
Author(s):  
Anna Buchman ◽  
Isaiah Shriner ◽  
Ting Yang ◽  
Junru Liu ◽  
Igor Antoshechkin ◽  
...  
Keyword(s):  
Gene Flow ◽  
Disease Vectors ◽  
Dependent Manner ◽  
Reproductive Barriers ◽  
Gene Drive ◽  
Wild Populations ◽  
Population Replacement ◽  
Practical Utility ◽  
Gene Drives ◽  
Isolated Species

AbstractEngineered reproductive species barriers are useful for impeding gene flow and driving desirable genes into wild populations in a reversible threshold-dependent manner. However, methods to generate synthetic barriers are lacking in advanced eukaryotes. To overcome this challenge, we engineered SPECIES (Synthetic Postzygotic barriers Exploiting CRISPR-based Incompatibilities for Engineering Species) to generate postzygotic reproductive barriers. Using this approach, we engineer multiple reproductively isolated SPECIES and demonstrate their threshold-dependent gene drive capabilities in D. melanogaster. Given the near-universal functionality of CRISPR tools, this approach should be portable to many species, including insect disease vectors in which confinable gene drives could be of great practical utility.One Sentence SummarySynthetically engineered SPECIES drive confinable population replacement.

scholarly journals Modeling the efficacy of CRISPR gene drive for schistosomiasis control

2021 ◽  
Author(s):  
Richard E Grewelle ◽  
Javier Perez-Saez ◽  
Josh Tycko ◽  
Erica KO Namigai ◽  
Chloe G Rickards ◽  
...  
Keyword(s):  
Genetic Model ◽  
Ecological Factors ◽  
Model Organisms ◽  
Snail Population ◽  
Gene Drive ◽  
Intermediate Hosts ◽  
Multiple Alleles ◽  
Sexual And Asexual Reproduction ◽  
Models Of Disease ◽  
Gene Drives

CRISPR gene drives could revolutionize the control of infectious diseases by accelerating the spread of engineered traits that limit parasite transmission in wild populations. While much effort has been spent developing gene drives in mosquitoes, gene drive technology in molluscs has received little attention despite the role of freshwater snails as obligate, intermediate hosts of parasitic flukes causing schistosomiasis -- a disease of poverty affecting more than 200 million people worldwide. A successful drive in snails must overcome self-fertilization, which prevents a drive's spread. Simultaneous hermaphroditism is a feature of snails -- distinct from gene drive model organisms -- and is not yet incorporated in gene drive models of disease control. Here we developed a novel population genetic model accounting for snails' sexual and asexual reproduction, susceptibility to parasite infection regulated by multiple alleles, fitness differences between genotypes, and a range of drive characteristics. We then integrated this model with an epidemiological model of schistosomiasis transmission and snail population dynamics. Simulations showed that gene drive establishment can be hindered by a variety of biological and ecological factors, including selfing. However, our model suggests that, under a range of conditions, gene drive mediated immunity in snails could maintain rapid disease reduction achieved by annual chemotherapy treatment of the human population, leading to long-term elimination. These results indicate that gene drives, in coordination with existing public health measures, may become a useful tool to reduce schistosomiasis burden in selected transmission settings with effective CRISPR construct design and close evaluation of the genetic and ecological landscape.

scholarly journals Mechanism of circadian clock. The 2017 Nobel Prize in physiology or medicine

Kosmos ◽  
2018 ◽  
Vol 67 (2) ◽  
pp. 245-249
Author(s):  
Jadwiga M. Giebultowicz
Keyword(s):  
Nobel Prize ◽  
Molecular Mechanisms ◽  
Biological Clock ◽  
Basic Research ◽  
Fruit Fly ◽  
Short Review ◽  
Model Organisms ◽  
Biological Clocks ◽  
Medical Doctors ◽  
Daily Rhythms

Since 1901, the Nobel Prize has been awarded to scientists who have made the most important discoveries for the benefit of humanity. The 2017 Nobel Prize in Physiology or Medicine was awarded jointly to Jeffrey C. Hall, Michael Rosbash and Michael W. Young “for their discoveries of molecular mechanisms controlling the circadian rhythm.” It may be surprising to learn that those three scientists dedicated their entire careers to research on the fruit fly, Drosophila melanogaster. However, as their studies progressed, it became increasingly clear that the mechanism of the biological clock that they discovered in Drosophila is very similar to a timekeeping mechanism present in mammals, including humans. Through interdisciplinary work between scientists performing basic research on model organisms and medical doctors, we have learned over time that daily rhythms support human health while disruption of these rhythms is associated with a range of pathological disorders such as cardiovascular problems, metabolic, neurological, and many other diseases. This short review highlights critical milestones on the way to understanding biological clocks, focusing on the roles played by the three Nobel Prize winners.

scholarly journals Engineered reproductively isolated species drive reversible population replacement

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anna Buchman ◽  
Isaiah Shriner ◽  
Ting Yang ◽  
Junru Liu ◽  
Igor Antoshechkin ◽  
...  
Keyword(s):  
Gene Flow ◽  
Disease Vectors ◽  
Dependent Manner ◽  
Reproductive Barriers ◽  
Gene Drive ◽  
Wild Populations ◽  
Genetic Incompatibility ◽  
Population Replacement ◽  
Gene Drives ◽  
Isolated Species

AbstractEngineered reproductive species barriers are useful for impeding gene flow and driving desirable genes into wild populations in a reversible threshold-dependent manner. However, methods to generate synthetic barriers are lacking in advanced eukaryotes. Here, to overcome this challenge, we engineer SPECIES (Synthetic Postzygotic barriers Exploiting CRISPR-based Incompatibilities for Engineering Species), an engineered genetic incompatibility approach, to generate postzygotic reproductive barriers. Using this approach, we create multiple reproductively isolated SPECIES and demonstrate their reproductive isolation and threshold-dependent gene drive capabilities in D. melanogaster. Given the near-universal functionality of CRISPR tools, this approach should be portable to many species, including insect disease vectors in which confinable gene drives could be of great practical utility.

CRISPR-Clear: A Fieldable Detection Procedure for Potential CRISPR-Cas9 Gene Drive Based Bioweapons

2019 ◽  
Author(s):  
Anna C. Nieuwenweg ◽  
Martijn M. van Galen ◽  
Angelina Horsting ◽  
Jorrit W. Hegge ◽  
Aldrik Velders ◽  
...  
Keyword(s):  
Genetic Modification ◽  
Screening Method ◽  
Dna Amplification ◽  
Synthetic Gene ◽  
Rapid Progression ◽  
Gene Drive ◽  
Naked Eye ◽  
Amplification Technique ◽  
Specific Alteration ◽  
Gene Drives

<p>Rapid progression in genetic modification research has made gene editing increasingly cheaper and easier to use. CRISPR-Cas9 for example, allows for the specific alteration of the genome of an organism with relative simplicity and low costs. This raised a worrying question; can genetic modification techniques be used to create novel bioweapons? A specific scenario is the initiation of a synthetic gene drive for malicious purposes. A synthetic gene drive can be used to quickly spread a mutation through an entire population. This mutation could alter vectors in such a way that they will spread human diseases or eradicate essential organisms. Since a gene drive spreads efficiently through a population, timely detection is essential. Thus, a quick and field deployable screening method is needed to counteract the malicious use of gene drives. </p> <p>Here, we show a battery-operated, sensitive screening method, named CRISPR-Clear, for the detection of gene drive modified organisms. CRISPR-Clear is based on the combination of three components: 1) A DNA amplification technique known as loop-mediated isothermal amplification (LAMP) for detecting the presence of a gene drive; b) a portable battery-operated Arduino device which heats up the sample to allow DNA amplification, and c) a naked-eye visualization of the results. </p> <p>We designed and tested six LAMP primers targeting a Cas9 endonuclease-based gene drive, assembled a battery-operated Arduino device and tested the naked-eye visualization method. In addition, we were able to detect the presence of the Cas9 gene, extracted from a transformed bacteria, providing a proof-of-concept of the CRISPR-Clear device.</p>

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