{"id":11598,"date":"2025-11-11T16:08:48","date_gmt":"2025-11-11T15:08:48","guid":{"rendered":"https:\/\/rvh-synergie.org\/actualites\/la-therapie-genique-contre-la-drepanocytose-et-la-%ce%b2-thalassemie-agit-en-perturbant-la-structure-tridimensionnelle-du-genome\/"},"modified":"2025-11-11T16:08:50","modified_gmt":"2025-11-11T15:08:50","slug":"la-therapie-genique-contre-la-drepanocytose-et-la-%ce%b2-thalassemie-agit-en-perturbant-la-structure-tridimensionnelle-du-genome","status":"publish","type":"post","link":"https:\/\/rvh-synergie.org\/actualites\/la-therapie-genique-contre-la-drepanocytose-et-la-%ce%b2-thalassemie-agit-en-perturbant-la-structure-tridimensionnelle-du-genome\/","title":{"rendered":"La th\u00e9rapie g\u00e9nique contre la dr\u00e9panocytose et la \u03b2-thalass\u00e9mie agit en perturbant la structure tridimensionnelle du g\u00e9nome"},"content":{"rendered":"<div>\n<div class=\"article-gallery lightGallery\">\n<div data-thumb=\"https:\/\/scx1.b-cdn.net\/csz\/news\/tmb\/2025\/gene-therapy-for-sickl-1.jpg\" data-src=\"https:\/\/scx2.b-cdn.net\/gfx\/news\/2025\/gene-therapy-for-sickl-1.jpg\" data-sub-html=\"Credit: &lt;i&gt;Blood&lt;\/i&gt; (2025). DOI: 10.1182\/blood.2025030211\">\n<figure class=\"article-img\">\n<\/figure><\/div>\n<\/div>\n<p>Les scientifiques de l&rsquo;h\u00f4pital de recherche pour enfants St. Jude et de l&rsquo;universit\u00e9 Northwestern ont identifi\u00e9 une opportunit\u00e9 de traitement jusqu&rsquo;alors inconnue pour la dr\u00e9panocytose et la \u03b2-thalass\u00e9mie. La d\u00e9couverte, publi\u00e9e dans <i>Sang<\/i>repose sur une nouvelle compr\u00e9hension du fonctionnement de la th\u00e9rapie g\u00e9nique bas\u00e9e sur CRISPR.<\/p>\n<p>Dans ces th\u00e9rapies, CRISPR-Cas9 cible un \u00e9l\u00e9ment r\u00e9gulateur de l\u2019ADN, appel\u00e9 amplificateur, qui contr\u00f4le l\u2019expression de BCL11A, un g\u00e8ne cl\u00e9 responsable du passage de la production d\u2019h\u00e9moglobine des formes f\u0153tales aux formes adultes. Les chercheurs ont d\u00e9couvert que cela perturbait la structure tridimensionnelle du g\u00e9nome n\u00e9cessaire au maintien d\u2019un niveau \u00e9lev\u00e9 d\u2019expression de BCL11A dans les pr\u00e9curseurs des globules rouges.<\/p>\n<p>En cons\u00e9quence, BCL11A est r\u00e9duit au silence, conduisant \u00e0 la r\u00e9activation de l\u2019h\u00e9moglobine f\u0153tale, qui compense l\u2019h\u00e9moglobine adulte d\u00e9fectueuse dans la dr\u00e9panocytose et la \u03b2-thalass\u00e9mie. Les chercheurs ont en outre d\u00e9couvert que le ciblage d\u2019un ARN sp\u00e9cifique produit par l\u2019amplificateur BCL11A pourrait avoir des effets similaires \u00e0 ceux de la th\u00e9rapie g\u00e9nique.<\/p>\n<p>BCL11A r\u00e9prime l&rsquo;expression de l&rsquo;h\u00e9moglobine f\u0153tale, qui est g\u00e9n\u00e9ralement produite \u00e0 de faibles niveaux dans les globules rouges des adultes en bonne sant\u00e9. L&rsquo;inactivation de BCL11A peut r\u00e9activer l&rsquo;expression de l&rsquo;h\u00e9moglobine f\u0153tale, compensant ainsi l&rsquo;h\u00e9moglobine falciforme mutante dans la dr\u00e9panocytose ou la perte des g\u00e8nes de la \u03b2-globine dans la \u03b2-thalass\u00e9mie.<\/p>\n<p>Les th\u00e9rapies g\u00e9niques r\u00e9cemment approuv\u00e9es pour ces troubles utilisent l&rsquo;\u00e9dition du g\u00e9nome bas\u00e9e sur CRISPR pour cibler l&rsquo;amplificateur BCL11A dans les cellules souches sanguines, obtenant ainsi des r\u00e9sultats transformateurs pour les patients. Une compr\u00e9hension plus d\u00e9taill\u00e9e de la fa\u00e7on dont la th\u00e9rapie g\u00e9nique agit pour perturber l\u2019expression de BCL11A reste cependant une question en cours.<\/p>\n<p>Les co\u00fbts \u00e9lev\u00e9s, la disponibilit\u00e9 limit\u00e9e et les risques potentiels associ\u00e9s aux th\u00e9rapies g\u00e9niques actuelles les rendent inaccessibles \u00e0 la plupart des patients. Il est donc n\u00e9cessaire de d\u00e9velopper des approches alternatives, \u00e9volutives et abordables pour r\u00e9duire la charge globale de morbidit\u00e9.<\/p>\n<p>\u00ab\u00a0Notre motivation pour cette \u00e9tude \u00e9tait double\u00a0\u00bb, a d\u00e9clar\u00e9 l&rsquo;auteur co-correspondant Jian Xu, Ph.D., D\u00e9partement de pathologie de St. Jude et Centre d&rsquo;excellence pour les \u00e9tudes sur la leuc\u00e9mie. \u00ab\u00a0Premi\u00e8rement, pour d\u00e9couvrir comment l&rsquo;\u00e9dition du g\u00e9nome CRISPR inactive efficacement BCL11A pour la r\u00e9activation de l&rsquo;h\u00e9moglobine f\u0153tale. Et deuxi\u00e8mement, pour identifier des strat\u00e9gies th\u00e9rapeutiques plus rentables et plus accessibles.\u00a0\u00bb<\/p>\n<div class=\"article-gallery lightGallery\">\n<div data-thumb=\"https:\/\/scx1.b-cdn.net\/csz\/news\/tmb\/2025\/gene-therapy-for-sickl.jpg\" data-src=\"https:\/\/scx2.b-cdn.net\/gfx\/news\/2025\/gene-therapy-for-sickl.jpg\" data-sub-html=\"Co-corresponding author Jian Xu, PhD,\u00a0and co-first author Kaili Wang, PhD,\u00a0St. Jude Department of Pathology,\u00a0in\u00a0a collaborative\u00a0effort\u00a0with\u00a0Northwestern University,\u00a0found a novel treatment opportunity for sickle cell disease and\u00a0\u03b2-thalassemia\u00a0by probing the mechanism for\u00a0gene therapy.\u00a0 Credit: St. Jude Children's Research Hospital\">\n<figure class=\"article-img text-center\">\n            <img decoding=\"async\" src=\"https:\/\/rvh-synergie.org\/actualites\/wp-content\/uploads\/2025\/11\/1762873728_976_La-therapie-genique-contre-la-drepanocytose-et-la-\u03b2-thalassemie-agit.jpg\" alt=\"La th\u00e9rapie g\u00e9nique contre la dr\u00e9panocytose et la \u03b2-thalass\u00e9mie agit en perturbant la structure tridimensionnelle du g\u00e9nome\" title=\"L'auteur co-correspondant Jian Xu, PhD, et le co-premier auteur Kaili Wang, PhD, D\u00e9partement de pathologie de St. Jude, dans le cadre d'un effort de collaboration avec l'Universit\u00e9 Northwestern, ont d\u00e9couvert une nouvelle opportunit\u00e9 de traitement pour la dr\u00e9panocytose et la \u03b2-thalass\u00e9mie en sondant le m\u00e9canisme de la th\u00e9rapie g\u00e9nique. Cr\u00e9dit : H\u00f4pital de recherche pour enfants St. Jude\"><br \/>\n                     <\/figure>\n<\/p><\/div>\n<\/div>\n<h2>La th\u00e9rapie g\u00e9nique brise la structure tridimensionnelle de l&rsquo;ADN<\/h2>\n<p>L\u2019\u00e9quipe a \u00e9tudi\u00e9 comment BCL11A est r\u00e9gul\u00e9 au cours de l\u2019h\u00e9matopo\u00ef\u00e8se (croissance des cellules sanguines) et a identifi\u00e9 un m\u00e9canisme de contr\u00f4le cl\u00e9 : la r\u00e9gion amplificatrice cibl\u00e9e par la th\u00e9rapie g\u00e9nique se repliait en une structure tridimensionnelle. \u00ab\u00a0Nous avons d\u00e9couvert que cet activateur forme une structure de &lsquo;rosette&rsquo; de chromatine, \u00e9tablissant de multiples contacts avec des \u00e9l\u00e9ments r\u00e9gulateurs critiques du g\u00e8ne\u00a0\u00bb, a expliqu\u00e9 Xu. \u00ab\u00a0Cela garantit une expression de haut niveau de BCL11A et emp\u00eache son inactivation dans les pr\u00e9curseurs des globules rouges.\u00a0\u00bb<\/p>\n<p>Lorsque CRISPR-Cas9 effectue une cassure de l\u2019ADN dans cet activateur dans le cadre de la th\u00e9rapie, il perturbe la structure de la rosette de chromatine. Sans cette structure, d\u2019autres prot\u00e9ines r\u00e9pressives peuvent p\u00e9n\u00e9trer et faire taire le g\u00e8ne BCL11A.<\/p>\n<p>De plus, les chercheurs ont d\u00e9couvert que la formation de cette structure complexe n\u00e9cessite un type sp\u00e9cial d\u2019ARN appel\u00e9 ARN \u00ab amplificateur \u00bb. Ils ont test\u00e9 si le ciblage de cet ARN amplificateur avec des oligonucl\u00e9otides antisens, un type de th\u00e9rapie plus rentable qui ne modifie pas le g\u00e9nome, pourrait produire le m\u00eame b\u00e9n\u00e9fice th\u00e9rapeutique.<\/p>\n<p>\u00ab\u00a0En administrant des oligonucl\u00e9otides antisens aux pr\u00e9curseurs des globules rouges normaux et falciformes, nous avons d\u00e9couvert que nous pouvons d\u00e9grader s\u00e9lectivement l&rsquo;ARN activateur, provoquant l&rsquo;inactivation du BCL11A et la r\u00e9activation de l&rsquo;h\u00e9moglobine f\u0153tale\u00a0\u00bb, a d\u00e9clar\u00e9 Xu. \u00ab\u00a0Nous pensons que cela pourrait offrir une alternative plus abordable, plus accessible et plus \u00e9volutive aux th\u00e9rapies g\u00e9niques actuelles.\u00a0\u00bb<\/p>\n<p>                                        <!-- print only --><\/p><\/div>\n","protected":false},"excerpt":{"rendered":"<p>Les scientifiques de l&rsquo;h\u00f4pital de recherche pour enfants St. Jude et de l&rsquo;universit\u00e9 Northwestern ont<\/p>\n","protected":false},"author":1,"featured_media":11599,"comment_status":"closed","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[86],"tags":[7629,90,881,1064,5727,5673,2010,1063,7630,7628],"class_list":["post-11598","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-les-maladies","tag-agit","tag-contre","tag-drepanocytose","tag-genique","tag-genome","tag-perturbant","tag-structure","tag-therapie","tag-tridimensionnelle","tag-thalassemie","generate-columns","tablet-grid-50","mobile-grid-100","grid-parent","grid-50","resize-featured-image"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v23.4 - 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