{"id":6434,"date":"2021-07-08T16:46:43","date_gmt":"2021-07-08T15:46:43","guid":{"rendered":"https:\/\/targetmalaria.org\/analysing-off-target-effects-in-crispr-based-gene-drive-mosquitoes\/"},"modified":"2023-08-15T15:00:32","modified_gmt":"2023-08-15T14:00:32","slug":"analysing-off-target-effects-in-crispr-based-gene-drive-mosquitoes","status":"publish","type":"post","link":"https:\/\/targetmalaria.org\/fr\/latest\/blog\/analysing-off-target-effects-in-crispr-based-gene-drive-mosquitoes\/","title":{"rendered":"Analyse des effets hors-cible sur les moustiques \u00e0 impulsion g\u00e9n\u00e9tique bas\u00e9e sur CRISPR\/Cas9"},"content":{"rendered":"\n<p>Le caract\u00e8re polyvalent de l\u2019outil d\u2019\u00e9dition du g\u00e9nome CRISPR-Cas9, <a href=\"https:\/\/www.nature.com\/articles\/d41586-020-02765-9\" target=\"_blank\" rel=\"noreferrer noopener\">mis au point initialement par les deux scientifiques<\/a> Emmanuelle Charpentier et Jennifer Doudna, r\u00e9compens\u00e9es par le prix Nobel, a permis le d\u00e9veloppement de syst\u00e8mes \u00e0 impulsion g\u00e9n\u00e9tique d\u00e9tenant un \u00e9norme potentiel pour la lutte anti-vectorielle. En tant que m\u00e9thode d\u2019\u00e9dition du g\u00e9nome, CRISPR-Cas9 est plus facile \u00e0 utiliser, plus rapide \u00e0 d\u00e9velopper et plus pr\u00e9cis que les techniques ant\u00e9rieures disponibles, et permet aux chercheurs d\u2019\u00e9diter le g\u00e9nome du moustique vecteur du paludisme avec un degr\u00e9 de pr\u00e9cision et d\u2019exactitude relativement \u00e9lev\u00e9.<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"alignright size-medium is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/targetmalaria.org\/wp-content\/uploads\/2021\/07\/Anopheles-Target-Malaria-300x200.jpg\" alt=\"\" class=\"wp-image-6120\" width=\"479\" height=\"319\" srcset=\"https:\/\/targetmalaria.org\/wp-content\/uploads\/2021\/07\/Anopheles-Target-Malaria-300x200.jpg 300w, https:\/\/targetmalaria.org\/wp-content\/uploads\/2021\/07\/Anopheles-Target-Malaria-1024x683.jpg 1024w, https:\/\/targetmalaria.org\/wp-content\/uploads\/2021\/07\/Anopheles-Target-Malaria-768x512.jpg 768w, https:\/\/targetmalaria.org\/wp-content\/uploads\/2021\/07\/Anopheles-Target-Malaria-1536x1024.jpg 1536w, https:\/\/targetmalaria.org\/wp-content\/uploads\/2021\/07\/Anopheles-Target-Malaria-2048x1366.jpg 2048w\" sizes=\"auto, (max-width: 479px) 100vw, 479px\" \/><figcaption><span class=\"has-inline-color has-white-color\">___<\/span><sup><em>Anopheles gambiae<\/em> mosquitoes<\/sup><\/figcaption><\/figure><\/div>\n\n\n\n<p>Au fur et \u00e0 mesure que la recherche avance dans ce domaine et que la faisabilit\u00e9 de l\u00e2chers dans l\u2019environnement de nos moustiques \u00e0 impulsion g\u00e9n\u00e9tique devient plus probable, il est important d\u2019\u00e9valuer non seulement les b\u00e9n\u00e9fices potentiels de cette nouvelle technologie, mais aussi les \u00e9ventuels risques qui pourraient d\u00e9couler de son utilisation. Si CRISPR-Cas9 arrive \u00e0 couper pr\u00e9cis\u00e9ment des s\u00e9quences cibl\u00e9es du g\u00e9nome, dans certaines circonstances, on a signal\u00e9 que des s\u00e9quences semblables mais \u00ab\u00a0hors-cible\u00a0\u00bb pouvaient \u00eatre coup\u00e9es ailleurs dans le g\u00e9nome. En th\u00e9orie, le fait d\u2019\u00e9diter ainsi des s\u00e9quences hors-cible pourrait causer des mutations ind\u00e9sirables dans la souche \u00e0 impulsion g\u00e9n\u00e9tique. Dans la majorit\u00e9 des cas, on peut raisonnablement anticiper que des \u00e9ditions hors-cible n\u2019entra\u00eeneront aucun changement au niveau de l\u2019organisme et ne sont donc pas automatiquement pr\u00e9judiciables. Il n\u2019emp\u00eache que si des mutations hors-cible induites par CRISPR-Cas9 se produisent dans les souches \u00e0 impulsion g\u00e9n\u00e9tique, comprendre ce ph\u00e9nom\u00e8ne constitue un aspect important de l\u2019\u00e9valuation pr\u00e9alable des risques avant qu\u2019un l\u00e2cher potentiel de terrain puisse \u00eatre envisag\u00e9.<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"alignleft size-large is-resized\"><a href=\"https:\/\/www.pnas.org\/content\/118\/22\/e2004838117\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/targetmalaria.org\/wp-content\/uploads\/2021\/07\/Screenshot-2021-07-08-at-16.58.07-778x1024.png\" alt=\"\" class=\"wp-image-6115\" width=\"207\" height=\"272\" srcset=\"https:\/\/targetmalaria.org\/wp-content\/uploads\/2021\/07\/Screenshot-2021-07-08-at-16.58.07-778x1024.png 778w, https:\/\/targetmalaria.org\/wp-content\/uploads\/2021\/07\/Screenshot-2021-07-08-at-16.58.07-228x300.png 228w, https:\/\/targetmalaria.org\/wp-content\/uploads\/2021\/07\/Screenshot-2021-07-08-at-16.58.07-768x1011.png 768w, https:\/\/targetmalaria.org\/wp-content\/uploads\/2021\/07\/Screenshot-2021-07-08-at-16.58.07-300x395.png 300w, https:\/\/targetmalaria.org\/wp-content\/uploads\/2021\/07\/Screenshot-2021-07-08-at-16.58.07.png 1142w\" sizes=\"auto, (max-width: 207px) 100vw, 207px\" \/><\/a><\/figure><\/div>\n\n\n\n<p><br><a href=\"https:\/\/www.pnas.org\/content\/118\/22\/e2004838117\" target=\"_blank\" rel=\"noreferrer noopener\">Un nouveau papier<\/a>, r\u00e9dig\u00e9 par notre \u00e9quipe de chercheurs \u00e0 Imperial College London et publi\u00e9 dans le magazine PNAS, explore le ph\u00e9nom\u00e8ne des effets hors-cible. Nous cherchions \u00e0 comprendre l\u2019impact que pourrait avoir la conception des transg\u00e8nes \u00e0 impulsion g\u00e9n\u00e9tique sur les effets hors-cible, et si CRISPR\/Cas9 pourrait induire des mutations hors-cible significatives dans nos souches \u00e0 impulsion g\u00e9n\u00e9tique.<\/p>\n\n\n\n<p><br>En collaboration avec des \u00e9quipes du <a href=\"https:\/\/www.massgeneral.org\/\" target=\"_blank\" rel=\"noreferrer noopener\">Massachusetts General Hospital<\/a>, nous avons identifi\u00e9 \u00e0 partir d\u2019\u00e9tudes mol\u00e9culaires une liste de sites hors-cible potentiels dans diverses souches \u00e0 impulsion g\u00e9n\u00e9tique que nous avions pr\u00e9c\u00e9demment g\u00e9n\u00e9r\u00e9es en laboratoire. Ces sites potentiels hors-cible ont \u00e9t\u00e9 analys\u00e9s par des moyens bio-informatiques puis par s\u00e9quen\u00e7age exhaustif, pour voir si des mutations \u00e9taient d\u00e9tect\u00e9es dans les g\u00e9nomes de nos souches \u00e0 impulsion g\u00e9n\u00e9tique.<\/p>\n\n\n\n<p><br><a href=\"https:\/\/www.nature.com\/articles\/nbt.3439\">Dans l\u2019une de nos souches initiales \u00e0 impulsion g\u00e9n\u00e9tique bas\u00e9e sur CRISPR<\/a>, nous avons observ\u00e9 des mutations hors-cible \u00e0 faible fr\u00e9quence, mais sans trouver aucun \u00e9l\u00e9ment sugg\u00e9rant des capacit\u00e9s d\u2019accumulation dans une population de moustiques, en d\u00e9pit d\u2019une exposition \u00e0 CRISPR\/Cas9 sur plusieurs g\u00e9n\u00e9rations. D\u2019ailleurs, dans notre <a href=\"https:\/\/www.nature.com\/articles\/nbt.4245\/\" target=\"_blank\" rel=\"noreferrer noopener\">souche \u00e0 impulsion g\u00e9n\u00e9tique de conception plus r\u00e9cente bas\u00e9e sur <em>doublesex<\/em><\/a>, nous n\u2019avons d\u00e9tect\u00e9 aucune mutation hors-cible. Les effets hors-cible doivent donc \u00eatre \u00e9valu\u00e9s au cas par cas pour chaque souche de moustiques porteuse d\u2019un transg\u00e8ne \u00e0 impulsion g\u00e9n\u00e9tique. En comparant les caract\u00e9ristiques des transg\u00e8nes dans ces diff\u00e9rentes souches, nous avons pu conclure que la conception s\u00e9lective de la s\u00e9quence de l\u2019ARN guide, tout en contraignant strictement dans le temps l\u2019expression de Cas9, permet d\u2019obtenir des souches \u00e0 impulsion g\u00e9n\u00e9tique bas\u00e9e sur CRISPR qui ne pr\u00e9sentent aucune mutation hors-cible d\u00e9celable.<\/p>\n\n\n\n<p><br>Cette \u00e9tude montre qu\u2019il est possible de r\u00e9duire \u00e0 des niveaux ind\u00e9celables les cas d\u2019\u00e9dition hors-cible avec CRISPR-Cas9 dans le contexte de l\u2019impulsion g\u00e9n\u00e9tique chez le moustique, \u00e0 condition de s\u2019appuyer sur la conception appropri\u00e9e des transg\u00e8nes; cela contribue de mani\u00e8re importante \u00e0 l\u2019\u00e9valuation des risques de l\u2019utilisation potentielle de nos souches \u00e0 impulsion g\u00e9n\u00e9tique sur le terrain pour lutter contre les vecteurs du paludisme.<\/p>\n\n\n\n<div style=\"height:51px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n","protected":false},"excerpt":{"rendered":"<p>Le caract\u00e8re polyvalent de l\u2019outil d\u2019\u00e9dition du g\u00e9nome CRISPR-Cas9, mis au point initialement par les deux scientifiques Emmanuelle Charpentier et Jennifer Doudna, r\u00e9compens\u00e9es par le prix Nobel, a permis le d\u00e9veloppement de syst\u00e8mes \u00e0 impulsion g\u00e9n\u00e9tique d\u00e9tenant un \u00e9norme potentiel pour la lutte anti-vectorielle. En tant que m\u00e9thode d\u2019\u00e9dition du g\u00e9nome, CRISPR-Cas9 est plus facile [&hellip;]<\/p>\n","protected":false},"author":32,"featured_media":6110,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","featured_image_focal_point":[],"_image_focal_point":[],"footnotes":""},"categories":[113],"profile_tax":[],"class_list":["post-6434","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-blog","post_writers-william-garrood","post_writers-william-garrood-fr"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Analyse des effets hors-cible sur les moustiques \u00e0 impulsion g\u00e9n\u00e9tique bas\u00e9e sur CRISPR\/Cas9 - Target Malaria<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/targetmalaria.org\/fr\/latest\/blog\/analysing-off-target-effects-in-crispr-based-gene-drive-mosquitoes\/\" \/>\n<meta property=\"og:locale\" content=\"fr_FR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Analyse des effets hors-cible sur les moustiques \u00e0 impulsion g\u00e9n\u00e9tique bas\u00e9e sur CRISPR\/Cas9 - Target Malaria\" \/>\n<meta property=\"og:description\" content=\"Le caract\u00e8re polyvalent de l\u2019outil d\u2019\u00e9dition du g\u00e9nome CRISPR-Cas9, mis au point initialement par les deux scientifiques Emmanuelle Charpentier et Jennifer Doudna, r\u00e9compens\u00e9es par le prix Nobel, a permis le d\u00e9veloppement de syst\u00e8mes \u00e0 impulsion g\u00e9n\u00e9tique d\u00e9tenant un \u00e9norme potentiel pour la lutte anti-vectorielle. 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