Keywords: Cas 9

Systematic identification of plausible pathways to potential harm via problem formulation for investigational releases of a population suppression gene drive to control the human malaria vector Anopheles gambiae in West Africa

J. B. Connolly, J. D. Mumford, S. Fuchs, G. Turner, C. Beech, A. R. North and A. Burt,  Malaria Journal,  20:170. 2021.
Population suppression gene drive has been proposed as a strategy for malaria vector control. A CRISPR-Cas9-based transgene homing at the doublesex locus (dsxFCRISPRh) has recently been shown to increase rapidly in frequency in, and suppress, caged laboratory populations of the ...
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Driving to Safety: CRISPR-Based Genetic Approaches to Reducing Antibiotic Resistance

E. Bier and V. Nizet,  Trends in Genetics,  2021.
The complex and challenging problem of reducing antibiotic resistance (AR) requires a network of both societal and science-based solutions to preserve the most lifesaving pharmaceutical intervention known to medicine. In addition to developing new classes of antibiotics, it is ...
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Ultra-conserved sequences in the genomes of highly diverse Anopheles mosquitoes, with implications for malaria vector control

S. M. O'Loughlin, A. J. Forster, S. Fuchs, T. Dottorini, T. Nolan, A. Crisanti and A. Burt,  G3-Genes Genomes Genetics,  2021.
Here we search for conserved sequences of 18bp and over in an alignment of 21 Anopheles genomes, spanning an evolutionary timescale of 100 million years, and characterise the resulting sequences according to their location and function. Over 8000 ultra-conserved elements were ...
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Meiotic Cas9 expression mediates genotype conversion in the male and female mouse germline.

A. J. Weitzel, H. A. Grunwald, R. Levina, V. M. Gantz, S. M. Hedrick, E. Bier and K. L. Cooper,  2021.03.16.435716,  2021.
We previously showed that such a system of genotype conversion from heterozygous to homozygous after a sequence targeted CRISPR/Cas9 double strand DNA break is feasible in the female mouse germline. In the male germline, however, all double strand breaks were instead repaired by ...
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Genetically Encoded CRISPR components Yield Efficient Gene Editing in the Invasive Pest, Drosophila suzukii

N. P. Kandul, E. J. Belikoff, J. Liu, A. Buchman, F. Li, A. Yamamoto, T. Yang, I. Shriner, M. J. Scott and O. Akbari,  bioRxiv,  2021.03.15.435483. 2021.
Here we have developed transgenic strains that encode three different terminators and four different promoters to express Cas9 in both the soma and/or germline of SWD. The Cas9 lines were evaluated through genetic crossing to transgenic lines that encode single guide RNAs ...
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Gene Drives Built to Follow More Stringent Rules of the Road

Anonymous,  Genetic Engineering & Biotechnology News,  2021.
Gene drives, or systems that accelerate the spread of desirable genetic traits into a population, may be built to achieve specific levels of spread when released into the wild. By exerting control over the degree of spread, those who unleash gene drives may realize the benefits ...
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New gene-drive technologies can help control crop pests

Anonymous,  AZO Life Sciences,  2021.
The supposed gene drives, which exploit CRISPR technology to affect genetic inheritance, show the potential to quickly spread particular genetic traits across the populations of a specified species. For instance, gene-drive technologies used on insects are being developed to stop ...
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New ‘Split-drive’ System Puts Scientists in the (Gene) Driver Seat

M. Aguilera,  UC San Diego News Center,  2021.
Gene-drive technologies applied in insects, for example, are being designed to halt the spread of devastating diseases such as malaria and dengue by preventing mosquito hosts from becoming infected. In agricultural fields, gene-drives are being developed to help control or ...
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A confinable home and rescue gene drive for population modification

N. P. Kandul, J. Liu, J. B. Bennett, J. M. Marshall and O. S. Akbari,  eLife,  10:e65939. 2021.
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 ...
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Developing GDi-CRISPR System for Multi-copy Integration in Saccharomyces cerevisiae

Z.-X. Zhang, Y.-Z. Wang, Y.-S. Xu, X.-M. Sun and H. Huang,  Applied Biochemistry and Biotechnology,  2021.
This study aims to develop a low-cost and easy-to-use multi-copy integration tool in S. cerevisiae. Firstly, twenty-one Cas proteins from different microorganisms were tested in S. cerevisiae to find the functional Cas proteins with optimal cleavage ability. Results showed that ...
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Designing gene drives to limit spillover to non-target populations

G. Greenbaum, M. W. Feldman, N. A. Rosenberg and J. Kim,  PLOS Genetics,  17:e1009278. 2021.
We develop mathematical models of gene-drive dynamics that incorporate migration between a target and non-target populations to investigate the possibility of effectively applying a gene drive in the target population while limiting its spillovers to the non-target population ...
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Split versions of Cleave and Rescue selfish genetic elements for measured self limiting gene drive

G. Oberhofer, T. Ivy and B. A. Hay,  PLoS genetics,  17:e1009385. 2021.
Self-sustaining Cleave and Rescue (ClvR) elements include a DNA sequence-modifying enzyme such as Cas9/gRNAs that disrupts endogenous versions of an essential gene, a tightly linked recoded version of the essential gene resistant to cleavage (the Rescue), and a Cargo. ClvR ...
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Optimized CRISPR tools and site-directed transgenesis in Culex quinquefasciatus mosquitoes for gene drive development

X. Feng, V. Lopez Del Amo, E. Mameli, M. Lee, A. L. Bishop, N. Perrimon and V. M. Gantz,  bioRxiv,  2021.02.10.430702. 2021.
Here, we developed a Culex-specific Cas9/gRNA expression toolkit and used site-directed homology-based transgenesis to generate and validate a Culex quinquefasciatus Cas9-expressing line. We showed that gRNA scaffold variants improve transgenesis efficiency in both Culex and ...
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A Code of Ethics for Gene Drive Research

G. J. Annas, C. L. Beisel, K. Clement, A. Crisanti, S. Francis, M. Galardini, R. Galizi, J. Grünewald, G. Immobile, A. S. Khalil, R. Müller, V. Pattanayak, K. Petri, L. Paul, L. Pinello, A. Simoni, C. Taxiarchi and J. K. Joung,  The CRISPR Journal,  2021.
A code of ethics can be a useful tool for all parties involved in the development and regulation of gene drives and can be used to help ensure that a balanced analysis of risks, benefits, and values is taken into consideration for the interest of society and humanity. We have ...
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Assisting Evolution: How Far Should We Go to Help Species Adapt?

E. Kolbert,  YaleEnvironment360,  2021.
It was a hot, intensely blue day in the Australian Outback, about 350 miles north of Adelaide. I was tagging along with Moseby as she checked the batteries on the motion-sensitive cameras that dot Arid Recovery, an ecosystem restoration project she and her husband launched in ...
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Should we dim the sun? Will we even have a choice

E. Klein,  New York Times,  2021.
“Under a White Sky” is going to be on my best books of 2021 list. It’s a wonderful work. Kolbert is the Pulitzer Prize-winning author of “The Sixth Extinction,” which you may have read. She is a staff writer at The New Yorker and just one of the great science ...
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In Our Image: The Ethics of CRISPR Genome Editing

J. C. Eissenberg,  Biomolecular Concepts,  12:1-7. 2021.
Here, I discuss the ethics surrounding the transformative CRISPR/Cas9mediated genome editing technology in the contexts of human genome editing to eradicate genetic disease and of gene drive technology to eradicate animal vectors of human disease.
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CRISPR and the splice to survive: New gene-editing technology could be used to save species from extinction—or to eliminate them.

E. Kolbert,  New Yorker,  2021.
About a year ago, not long before the pandemic began, I paid a visit to the center, which is an hour southwest of Melbourne. The draw was an experiment on a species of giant toad known familiarly as the cane toad. The toad was introduced to Australia as an agent of pest control, ...
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Control of malaria-transmitting mosquitoes using gene drives

T. Nolan,  Philosophical Transactions of the Royal Society B: Biological Sciences,  376:20190803. 2020.
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 ...
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Vector dynamics influence spatially imperfect genetic interventions against disease

M. K. Yuksel, C. H. Remien, B. Karki, J. J. Bull and S. M. Krone,  Evolution, Medicine, and Public Health,  9:1-10. 2020.
In spatially structured populations, imperfect coverage of the vector will leave pockets in which the parasite may persist. Movement by humans may disrupt this local persistence and facilitate eradication when these pockets are small, spreading parasite reproduction outside ...
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New insect species made via genetic engineering

L. Leffer,  SCIENCELINE,  2020.
A biotech fast-forward button for evolution is on the horizon. Researchers say they have used a novel genetic engineering method to create several new species of fruit fly in the lab for the first time — an achievement which might help put a future without malaria and other ...
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A CRISPR endonuclease gene drive reveals two distinct mechanisms of inheritance bias

S. A. N. Verkuijl, E. González, J. X. D. Ang, M. Li, N. P. Kandul, M. Anderson, O. S. Akbari, M. Bonsall and L. Alphey,  bioRxiv,  2020.12.15.421271. 2020.
In this study, we report the functioning of sds3, bgcn, and nup50 expressed Cas9 in an Aedes aegypti homing split drive system targeting the white gene. We report their inheritance biasing capability, propensity for maternal deposition, and zygotic/somatic expression. ...
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Mosquito population modification: the drive to malaria eradication

A. A. James,  BugBitten BMC,  2020.
We have had considerable success in the past demonstrating that we can use modern molecular biological and insect transgenesis tools to make genes that prevent mosquitoes from passing on parasites (see 1 and 2). We have focused most recently on laboratory experiments to find ways ...
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Gene drive blocks malaria transmission in mosquitoes

labonline,  labonline,  2020.
Employing a strategy known as ‘population modification’, which involves using a CRISPR-Cas9 gene drive system to introduce genes preventing parasite transmission into mosquito chromosomes, University of California (UC) researchers have made a major advance in the use of ...
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Evading evolution of resistance to gene drives

R. Gomulkiewicz, M. L. Thies and J. J. Bull,  bioRxiv,  2020.08.27.270611. 2020.
Our analyses suggest that among gene drives that cause moderate suppression, toxin-antidote systems are less apt to select for resistance than homing drives. Single drives of this type would achieve only partial population suppression, but multiple drives (perhaps delivered ...
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A gene-drive rescue system for the modification of malaria mosquito populations

A. Adolfi,  Nature Research Bioengineering Community,  2020.
Mosquito populations can now be reliably modified using 1) antimalarial molecules that block parasite development and 2) a CRISPR-based gene drive system that mediates their rapid spreading across the vector population.
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UC researchers pioneer more effective method of blocking malaria transmission in mosquitoes

UCI,  UCI News,  2020.
University of California, Irvine postdoctoral researcher Adriana Adolfi, in collaboration with colleagues at UCI, UC Berkeley and UC San Diego, followed up on the group’s pioneering effort to develop CRISPR-based gene drive systems for making mosquito vectors resistant to ...
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Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

A. Adolfi, V. M. Gantz, N. Jasinskiene, H.-F. Lee, K. Hwang, G. Terradas, E. A. Bulger, A. Ramaiah, J. B. Bennett, J. J. Emerson, J. M. Marshall, E. Bier and A. A. James,  Nature Communications,  11:5553. 2020.
Here, we develop a recoded gene-drive rescue system for population modification of the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant ...
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Gene Drive: The What, How, Why, and Whether We Should

N. Pazhayam,  The Pipettepen,  2020.
Under regular Mendelian inheritance, the probability of inheriting a particular allele from a heterozygous parent is 50% – this is because offspring can only inherit one or the other chromosome from each parent. However, gene drive is a technology that changes this probability ...
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WHO Refers to GM Mosquitoes as Beneficial Technology

ISAAA,  Crop Biotech Update,  2020.
The World Health Organization (WHO) released its official statement to clarify its stance on the evaluation and use of genetically modified (GM) mosquitoes and its use to control vector-borne diseases (VBD). WHO says it supports the investigation of all potentially beneficial ...
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Position of ARRIGE Scientific Committee on Gene Drive

ARRIGE Scientific Committee on Gene Drive,  ARRIGE Newsletter,  2020.
We are facing a change of paradigm that must lead us to be responsible for altered inheritance and the hybridization between artefacts, considered as natural or artificial, at the very moment when this division itself is blurred by the engineering capacity to act on mutations, ...
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Progress Toward Zygotic and Germline Gene Drives in Mice

C. Pfitzner, M. A. White, S. G. Piltz, M. Scherer, F. Adikusuma, J. N. Hughes and P. Q. Thomas,  The CRISPR Journal,  3:388-397. 2020.
Here, we investigated the efficiency of CRISPR-Cas9-based gene drives in Mus musculus by constructing "split drive" systems where gRNA expression occurs on a separate chromosome to Cas9, which is under the control of either a zygotic (CAG) or germline (Vasa) promoter.
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Engineered Gene Drives: State of Research Webinar Series by The GeneConvene Global Collaborative September-October 2020

David O'Brochta and Hector Quemada,  GeneConvene Global Collaborative,  2020.
A series of technical webinars on engineered gene drive technology research and development given by leading researchers in the field.
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Inherently confinable split-drive systems in Drosophila

G. Terradas, A. B. Buchman, J. B. Bennett, I. Shriner, J. M. Marshall, O. S. Akbari and E. Bier,  bioRxiv,  2020.09.03.282079. 2020.
Here, we test split gene-drive (sGD) systems in Drosophila melanogaster that were inserted into essential genes required for viability (rab5, rab11, prosalpha2) or fertility (spo11). I
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Chromosome drives via CRISPR-Cas9 in yeast

H. Xu, M. Han, S. Zhou, B.-Z. Li, Y. Wu and Y.-J. Yuan,  Nature Communications,  11:4344. 2020.
Our results show that the entire Saccharomyces cerevisiae chromosome can be eliminated efficiently through only one double-strand break around the centromere via CRISPR-Cas9. As a proof-of-concept experiment of this CRISPR-Cas9 chromosome drive system, the synthetic yeast ...
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Evading evolution of resistance to gene drives

R. Gomulkiewicz, M. L. Thies and J. J. Bull,  bioRxiv,  2020.
Here we develop mathematical and computational models to identify conditions under which suppression drives will evade resistance, even if resistance is present initially.
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Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae

R. Carballar-Lejarazú, C. Ogaugwu, T. Tushar, A. Kelsey, T. B. Pham, J. Murphy, H. Schmidt, Y. Lee, G. C. Lanzaro and A. A. James,  Proceedings of the National Academy of Sciences,  202010214. 2020.
We show here that the Cas9/guide RNA-based gene-drive components of a genetically-engineered malaria mosquito vector, Anopheles gambiae, achieve key target product profile requirements for efficacy and performance.
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A home and rescue gene drive forces its inheritance stably persisting in populations

N. P. Kandul, J. Liu, J. B. Bennett, J. M. Marshall and O. Akbari,  bioRxiv,  2020.08.21.261610. 2020.
We demonstrate that HomeR can achieve nearly ~100% transmission enabling it to persist at genotypic fixation in several multi-generational population cage experiments, underscoring its long term stability.
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Modelling the suppression of a malaria vector using a CRISPR-Cas9 gene drive to reduce female fertility

A. R. North, A. Burt and H. C. J. Godfray,  BMC Biology,  18:98. 2020.
Gene drives based on CRISPR-Cas9 technology are increasingly being considered as tools for reducing the capacity of mosquito populations to transmit malaria, and one of the most promising options is driving endonuclease genes that reduce the fertility of female mosquitoes. Here, ...
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Meet Cosmo, the gene-edited Crispr calf

S. D. McClain,  Capital Press,  2020.
Cosmo was the grand finale of a series of experiments to create a line of genome-edited cattle tailored for the beef industry. He was designed to produce 75% male offspring.
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Can a population targeted by a CRISPR-based homing gene drive be rescued?

N. O. Rode, V. Courtier-Orgogozo and F. Débarre,  G3-Genes Genomes Genetics,  2020.
N. O. Rode, V. Courtier-Orgogozo and F. Débarre (2020). G3 doi: 10.1534/g3.120.401484 Developing countermeasures is important to control the spread of gene drives, should they result in unanticipated damages. One proposed countermeasure is the introduction of individuals ...
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The future of beef might be a sausage fest

N. Johnson,  grist,  2020.
N. Johnson. (2020) grist. A media report on the creation of a cow with a sex ratio altering genetic change expected to lead to 3/4 of the cow's offspring being males. This type of sex ratio distortion results in gene drive and is also being considered to help control populations ...
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Meet Cosmo the Frankenbull: Scientists genetically engineer a bull calf so that 75 per cent of its offspring will be male

J. Pinkstone,  Daily Mail,  2020.
J. Pinkstone (2020). Daily Mail. A media report on the creation of a cow with a sex ratio altering genetic change expected to lead to 3/4 of the cow's offspring being males. This type of sex ratio distortion results in gene drive and is also being considered to help control ...
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Meet the first genetically modified bull. Why did scientists change it

J. Kessler,  Free News,  2020.
J. Kessler (2020). Free News. UC Davis scientists have successfully introduced a bovine embryo, or the bovine SRY gene, which is responsible for the development of the male. This is the first demonstration of targeted gene insertion for large DNA sequences through embryo-mediated ...
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Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives

V. López Del Amo, B. S. Leger, K. J. Cox, S. Gill, A. L. Bishop, G. D. Scanlon, J. A. Walker, V. M. Gantz and A. Choudhary,  Cell Reports,  31:107841. 2020.
Summary Synthetic CRISPR-based gene-drive systems have tremendous potential in public health and agriculture, such as for fighting vector-borne diseases or suppressing crop pest populations. These elements can rapidly spread in a population by breaching the inheritance limit of ...
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Development of zygotic and germline gene drives in mice

C. Pfitzner, J. N. Hughes, M. A. White, M. Scherer, S. G. Piltz and P. Q. Thomas,  bioRxiv,  2020.
Here we investigated the efficiency of CRISPR/Cas9-based gene drives in Mus musculus by constructing "split drive" systems with Cas9 under the control of zygotic (CAG) or germline (Vasa) promoters.
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Simulation models from: Can CRISPER-mediated gene drive work in pest and beneficial haplodiploid species?

J. Li and B. Tabashnik,  Dryad,  2020.
Gene drives based on CRISPR/Cas9 have the potential to reduce the enormous harm inflicted by crop pests and insect vectors of human disease, as well as to bolster valued species. In contrast with extensive empirical and theoretical studies in diploid organisms, little is known ...
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Malaria mosquitoes eliminated in lab by creating all male populations

H. Dunning,  Imperial College London,  2020.
A team led by Imperial College London spread a genetic modification that distorts the sex ratio through a population of caged Anopheles gambiae mosquitoes using ‘gene drive’ technology.
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Gene drive outcomes not determined by genetic variation – A Podcast

Thomas Locke,  Malaria Minute,  2020.
Gene drives are a system of genetic modification that use ‘molecular scissors’ to edit DNA sequences that self-perpetuate to ensure the rapid spread of mutation in a population. They offer new avenues for eradicating vector-borne diseases like malaria. They rely on the Cas9 ...
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Super-Mendelian inheritance mediated by CRISPR-Cas9 in the female mouse germline

H. A. Grunwald, V. M. Gantz, G. Poplawski, X.-r. S. Xu, E. Bier and K. L. Cooper,  TAGC 2020,  2020.
A gene drive biases the transmission of one of the two copies of a gene such that it is inherited more frequently than by random segregation. Highly efficient gene drive systems that have recently been developed in insects, which leverage the sequence-targeted DNA cleavage ...
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Gene drive and resilience through renewal with next generation Cleave and Rescue selfish genetic elements

G. Oberhofer, T. Ivy and B. A. Hay,  Proceedings of the National Academy of Sciences,  117:9013-9021. 2020.
Gene drive can spread beneficial traits through populations, but will never be a one-shot project in which one genetic element provides all desired modifications, for an indefinitely long time. Here, we show that gene drive-mediated population modification in Drosophila can be ...
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Can a population targeted by a CRISPR-based homing gene drive be rescued?

N. O. Rode, V. Courtier-Orgogozo and F. Débarre,  bioRxiv,  2020.03.17.995829. 2020.
CRISPR-based homing gene drive is a genetic control technique aiming to modify or eradicate natural populations through the release of individuals carrying an engineered piece of DNA that can be inherited by all their progeny. Developing countermeasures is important to control ...
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Anti-CRISPR protein applications: natural brakes for CRISPR-Cas technologies

Marino, N. D., Pinilla-Redondo, R. , Csorgo, B., Bondy-Denomy, J.,  Nature Methods,  2020.
Clustered, regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) genes, a diverse family of prokaryotic adaptive immune systems, have emerged as a biotechnological tool and therapeutic. The discovery of protein inhibitors of CRISPR-Cas systems, ...
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Population-level multiplexing: A promising strategy to manage the evolution of resistance against gene drives targeting a neutral locus

M. P. Edgington, T. Harvey-Samuel and L. Alphey,  Evolutionary Applications,  10. 2020.
CRISPR-based gene drives bias inheritance in their favour by inducing double-stranded breaks (DSBs) at wild-type homologous loci and using the drive transgene as a repair template-converting drive heterozygotes into homozygotes. Recent studies have shown that alternate ...
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The kill-switch for CRISPR that could make gene-editing safer

E. Dolgin,  Nature,  577:308-310. 2020.
How anti-CRISPR proteins and other molecules could bolster biosecurity and improve medical treatments.
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These are the 5 most dystopian technologies of 2020 and beyond

M. Sullivan,  FastCompany,  2019.
Tech is always both good and bad. But we live in a time when everything gets weaponized—ideas, images, ancient texts, biases, and even people. And technology provides the tools to do it easier, faster, and with less resources.
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What is genome editing?

NHGRI,  NHGRI,  2019.
Genome editing is a method that lets scientists change the DNA of many organisms, including plants, bacteria, and animals. Editing DNA can lead to changes in physical traits, like eye color, and disease risk. Scientists use different technologies to do this.
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CRISPR Explained

Mayo Clinic,  Mayo Clinic,  2018.
A short video that simply explains what CRISPR is and how it is used for gene editing. Simple language and highly accessible.
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Genome editing: scientific opportunities, public interests and policy options in the European Union

EASAC,  European Academies Science Advisory Council,  2017.
In many of the areas in which EASAC, the European Academies’ Science Advisory Council, works, where a large and solid body of knowledge is needed to inform the action of our societies, it is important to recognise that there is an intimate mix of science and values involved in ...
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