{"id":15969,"date":"2022-06-14T20:42:45","date_gmt":"2022-06-14T18:42:45","guid":{"rendered":"https:\/\/dupmecp2.eu\/reversione-dei-fenotipi-in-modelli-di-topi-mecp2-usando-oligonucleotidi-antisenso\/"},"modified":"2023-04-17T15:46:43","modified_gmt":"2023-04-17T15:46:43","slug":"reversion-of-fenotipi-in-top-models-mecp2-using-oligonucleotidi-antisenso","status":"publish","type":"post","link":"https:\/\/dupmecp2.eu\/es\/reversion-of-fenotipi-in-top-models-mecp2-using-oligonucleotidi-antisenso\/","title":{"rendered":"\"Reversione dei fenotipi in modelli di topi MECP2 using oligonucleotidi antisenso\"."},"content":{"rendered":"<p><strong>La Prof.ssa Huda Zoghbi y sus colaboradores del Baylor College of Medicine de Texas (EE.UU.) han publicado un art\u00edculo titulado \"Reversibilita' del fenotipo nel topo utilizzando il salvataggio genetico o oligonucleotidi antisenso\". Este art\u00edculo presenta los resultados del uso de oligonucle\u00f3tidos antisentido para corregir los niveles de MeCP2 y provocar una reversi\u00f3n de los trastornos conductuales, moleculares y el\u00e9ctricos en modelos animales con s\u00edndrome de duplicaci\u00f3n de MECP2.<\/strong><\/p>\n\n<p>Reversi\u00f3n de fenotipos en ratones con duplicaci\u00f3n de MECP2 mediante rescate gen\u00e9tico u oligonucle\u00f3tidos antisentido, Huda Zoghbi <em>et al,<\/em> <em>Naturaleza<\/em><strong> 528, <\/strong>123-126 (2015)<\/p>\n\n<p><\/p>\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n<p><\/p>\n\n<p><strong>REESCRITURA DEL ART\u00cdCULO:<\/strong><\/p>\n\n<p>Una variaci\u00f3n en el n\u00famero de copias del gen se ha asociado frecuentemente con retraso del desarrollo, discapacidad intelectual y alteraciones pertenecientes al espectro autista. El S\u00edndrome de Duplicaci\u00f3n MECP2 es una de las reordenaciones gen\u00f3micas m\u00e1s comunes en maschi y se caracteriza por autismo, discapacidad intelectual, deficiencias motoras, ansiedad, epilepsia, infecciones respiratorias frecuentes y muerte prematura.<\/p>\n\n<p>La amplia gama de d\u00e9ficits causados por la prote\u00edna MECP2 producida en exceso plantea un reto importante a los enfoques terap\u00e9uticos tradicionales basados en consideraciones bioqu\u00edmicas. Por consiguiente, hemos encontrado estrategias que tienen como objetivo directo la prote\u00edna MeCP2 y que son susceptibles de ser utilizadas en una terapia cl\u00ednica.<\/p>\n\n<p>La primera pregunta a la que hemos intentado dar una respuesta es si la disfunci\u00f3n neurol\u00f3gica puede ser reversible una vez que los s\u00edntomas son evidentes. La reversi\u00f3n del fen\u00f3meno en pacientes sintom\u00e1ticos adultos se ha demostrado en modelos de trastornos neurol\u00f3gicos debidos a p\u00e9rdida de funci\u00f3n monog\u00e9nica, como la p\u00e9rdida de MeCP2 en el s\u00edndrome de Rett. Esto indica que, incluso en algunos casos, la neuroanatom\u00eda puede estar lo suficientemente alterada como para que la correcci\u00f3n de la disfunci\u00f3n molecular en la base de estos trastornos pueda estabilizar una fisiolog\u00eda sana.<\/p>\n\n<p>Data l'assenza di neurodegenerazione nella Sindrome da Duplicazione di MECP2, noi proponiamo che il ripristino dei livelli normali di MeCP2 negli adulti di topi modello possa correggere il loro fenotipo.<\/p>\n\n<p>Creando y caracterizando un modelo de topo con prote\u00edna MeCP2 sobrante espressa, demostramos que la correcci\u00f3n de los niveles de MeCP2 invierte en gran parte el d\u00e9ficit comportamental, molecular y electrofisiol\u00f3gico.<\/p>\n\n<p>I livelli di MeCP2 sono stati ridotti utilizzando un oligonucleotide antisenso.<\/p>\n\n<p>Estas mol\u00e9culas son \u00e1cidos nucleicos modificados que pueden ibridizarse selectivamente con el ARN mensajero transcrito por un gen silenciador y se utilizan con \u00e9xito en diversos modelos de topo.<\/p>\n\n<p>Hemos descubierto que el tratamiento con oligonucle\u00f3tidos antisentido induce una recuperaci\u00f3n significativa del fenotipo en adultos transg\u00e9nicos con s\u00edntomas de enfermedad por duplicaci\u00f3n de MECP2 (MECP2-TG) y corrige los niveles de MeCP2 en las c\u00e9lulas linfoblastoides de pacientes con enfermedad por duplicaci\u00f3n de MECP2 en relaci\u00f3n con la dosis de oligonucle\u00f3tidos administrada.<\/p>\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n<p><\/p>\n\n<div class=\"wp-block-buttons is-layout-flex wp-block-buttons-is-layout-flex\">\n<div class=\"wp-block-button is-style-fill\"><a class=\"wp-block-button__link has-white-color has-text-color has-background wp-element-button\" href=\"https:\/\/www.nature.com\/articles\/nature16159\" style=\"border-radius:14px;background-color:#f7a13f\" target=\"_blank\" rel=\"noreferrer noopener\">A la publicaci\u00f3n<\/a><\/div>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>La Prof.ssa Huda Zoghbi e collaboratori al Baylor College of Medicine in Texas, USA hanno pubblicato un articolo intitolato \u201cReversibilita\u2019 del fenotipo nel topo utilizzando il salvataggio genetico o oligonucleotidi [&hellip;]<\/p>","protected":false},"author":1,"featured_media":13095,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[139],"tags":[],"class_list":["post-15969","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-pubblicazioni"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.8 - 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