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Open AccessJournal ArticleDOI

Agricultural pest control with CRISPR-based gene drive: time for public debate

TLDR
Gene drive technology to control disease vectors or pests has great potential for addressing humanitarian and public health problems, however, its application for pest control in agriculture raises important environmental, social and ethical issues.
Abstract
Gene drive based on the CRISPR/Cas‐9 gene editing system is a powerful technology that promotes the inheritance of the gene drive tool itself via sexual reproduction and can therefore spread quickly through a population. It holds great potential for public health and humanitarian purposes, such as reducing the burden of vector‐borne diseases like malaria. Here, we discuss another potential application of CRISPR‐based gene drive, namely the control of pest species to increase crop production. We argue that gene drive‐based pest control strategies should receive more attention from policymakers and the public given their enormous potential impact on the environment, their easy accessibility, and the current dearth of regulations. ### The CRISPR‐based gene drive technology CRISPR‐based gene drive, named here gene drive for short, allows the rapid spread of a DNA cassette into a target species. The cassette contains three elements: a gene encoding the bacterial Cas‐9 protein, a gene coding a guide RNA that targets a particular site in the genome and flanking sequences which allow the cassette to insert at a given target site [1], [2], [3]. This construct can copy and paste itself into a designed position within a genome, thereby propagating through a population. A normal allele has a 50% chance of being inherited by each offspring, but a gene drive cassette has more than 90% chance of being transmitted to the next generation owing to its ability to copy itself throughout the genome [1], [2], [3]. Gene drive can bypass the vagaries of evolution, by manipulating both heredity and mutations: it enhances its transmission to the next generation, and mutations happen exactly where the gene drive has been designed to cut, producing the desired DNA sequence. In theory, the release of just a few individuals within a population could lead …

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Journal ArticleDOI

Development of CRISPR-Cas systems for genome editing and beyond

TL;DR: A personal perspective on the development of CRISPR-Cas9 for genome editing within the broader context of the field is provided and the work to discover novel Cas effectors and develop them into additional molecular tools is discussed.
Journal ArticleDOI

Gene drive inhibition by the anti-CRISPR proteins AcrIIA2 and AcrIIA4 in Saccharomyces cerevisiae

TL;DR: Use of the AcrIIA2 and AcRIIA4 proteins are demonstrated to inhibit active gene drive systems in budding yeast and an unbiased mutational scan reveals that titration of Cas9 inhibition may be possible by modification of the anti-CRISPR primary sequence.
Journal ArticleDOI

Population management using gene drive: molecular design, models of spread dynamics and assessment of ecological risks

TL;DR: This work examines the challenges posed by the evolution of resistance to gene drives and review the various molecular and environmental risks associated with gene drives (e.g. propagation to non target populations or species and unintended detrimental ecosystem impacts).
Journal ArticleDOI

A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deployment.

TL;DR: A trans-complementing split-gene drive that requires inheritance of separate transgenes to assemble a fully functional drive and demonstrates its ability to promote super-Mendelian inheritance of the separate trans genes.
Journal ArticleDOI

Gene drive systems: do they have a place in agricultural weed management?

TL;DR: Modelling‐based studies can inform how and if gene drives could be employed in weed populations, and these studies are an essential first step towards determining the utility of gene drives for weed management.
References
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Journal ArticleDOI

A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae

TL;DR: Population modeling and cage experiments indicate that a CRISPR-Cas9 construct targeting one of these loci meets the minimum requirement for a gene drive targeting female reproduction in an insect population, which could expedite the development of gene drives to suppress mosquito populations to levels that do not support malaria transmission.
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Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi

TL;DR: A highly effective autonomous Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9)-mediated gene-drive system in the Asian malaria vector Anopheles stephensi, adapted from the mutagenic chain reaction (MCR).
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Concerning RNA-guided gene drives for the alteration of wild populations

TL;DR: The potential for RNA-guided gene drives based on the CRISPR nuclease Cas9 to serve as a general method for spreading altered traits through wild populations over many generations is considered.
Journal ArticleDOI

Site-specific selfish genes as tools for the control and genetic engineering of natural populations

TL;DR: The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.
Journal ArticleDOI

The mutagenic chain reaction: A method for converting heterozygous to homozygous mutations

TL;DR: In Drosophila, it is found that MCR mutations efficiently spread from their chromosome of origin to the homologous chromosome, thereby converting heterozygous mutations to homozygosity in the vast majority of somatic and germline cells.
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