{"id":15078,"date":"2022-06-14T20:42:45","date_gmt":"2022-06-14T20:42:45","guid":{"rendered":"https:\/\/dupmecp2.eu\/fenotipo-reversible-en-un-modelo-humanizado-en-ratones\/"},"modified":"2023-02-17T20:01:00","modified_gmt":"2023-02-17T20:01:00","slug":"odwracalne-fenotipo-w-modelu-humanizowanym-u-szczurow","status":"publish","type":"post","link":"https:\/\/dupmecp2.eu\/pl\/odwracalne-fenotipo-w-modelu-humanizowanym-u-szczurow\/","title":{"rendered":"Fenotipo reversible en un modelo humanizado en ratones"},"content":{"rendered":"<p><strong>Shao i wsp. z grupy prof. Zoghbi (Baylor College of Medicine, Texas, EE.UU.) opublikowali artyku\u0142 w Science Translational medicine zatytu\u0142owany \"Terapia oligonukleotydami antysentydowymi w humanizowanym modelu zespo\u0142u duplikacji MECP2 u szczur\u00f3w\". <\/strong><\/p>\n\n<p><strong>Ka\u017cdy gatunek posiada w\u0142asne geny, kt\u00f3re koduj\u0105 bia\u0142ka charakterystyczne wy\u0142\u0105cznie dla danego gatunku. Es posible que las prote\u00ednas humanas y de rat\u00f3n sean ligeramente diferentes. Model zastosowany w prezentowanej pracy, znany jako \"model humanizowany\", pozwala na lepsz\u0105 ocen\u0119 aktywno\u015bci oligonukleotyd\u00f3w antysensownych (ASO) specyficznie na bia\u0142ko ludzkie wytwarzane przez szczura. W zwi\u0105zku z tym, istnieje wi\u0119ksza szansa na przysz\u0142e zastosowanie ASO u ludzi.<\/strong><\/p>\n\n<p><strong>Niniejszy artyku\u0142 przedstawia wyniki uzyskane po dokomorowej iniekcji oligonukleotyd\u00f3w antysensownych w modelu powielania gen\u00f3w \"MECP2 humanizado\", w kt\u00f3rym szczur ma dwa ludzkie typy MECP2 i \u017cadnego endogennego.<\/strong><\/p>\n\n<p><strong>Podanie leku skutecznie zmniejszy\u0142o ekspresj\u0119 MECP2 w ca\u0142ym m\u00f3zgu tych szczur\u00f3w, z\u0142agodzi\u0142o r\u00f3\u017cne zaburzenia przewodnictwa i przywr\u00f3ci\u0142o ekspresj\u0119 niekt\u00f3rych gen\u00f3w regulowanych przez MeCP2 w spos\u00f3b zale\u017cny od dawki i bez jakiejkolwiek toksyczno\u015bci.<\/strong><\/p>\n\n<p>Terapia oligonukleotydami antysensownymi w humanizowanym mysim modelu zespo\u0142u duplikacji MECP2, Shao i in.<em>Sci. Transl. Med<\/em>. <strong>13<\/strong>, 7785 (2021)<\/p>\n\n<p><\/p>\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n<p><\/p>\n\n<p><strong>STRESZCZENIE PUBLIKACJI<\/strong><\/p>\n\n<p>Wiele form niepe\u0142nosprawno\u015bci intelektualnej wynika z r\u00f3\u017cnic w liczbie kopii i jak dot\u0105d nie ma sprawdzonych metod leczenia tej klasy zaburze\u0144. Zesp\u00f3\u0142 duplikacji MECP2 (MDS) jest jedn\u0105 z najcz\u0119stszych reordenamientos gen\u00f3micos u varones i wynika z duplikacji, kt\u00f3re naruszaj\u0105 locus del gen de la prote\u00edna de uni\u00f3n metil-CpG 2 (MECP2). Wcze\u015bniej wykazano, \u017ce terapia oligonukleotydami antysentydowymi (ASO) mo\u017ce zmniejszy\u0107 ilo\u015b\u0107 bia\u0142ka MeCP2 w modelu szczur\u00f3w z MDS i przywr\u00f3ci\u0107 cechy charakterystyczne choroby.<\/p>\n\n<p>Ten model u szczur\u00f3w z MDS, bez wzgl\u0119du na to, prezentowa\u0142 ludzki allel transgenu i szczurzy allel, kt\u00f3ry jako ostatni by\u0142 chroniony przez terapi\u0119 MECP2-ASO przeznaczon\u0105 specjalnie dla ludzi.<\/p>\n\n<p>Poniewa\u017c MeCP2 jest bia\u0142kiem wra\u017cliwym na dawk\u0119, ASO musi by\u0107 miareczkowane w taki spos\u00f3b, aby ilo\u015b\u0107 MeCP2 nie zosta\u0142a zbytnio zmniejszona, co spowodowa\u0142oby zesp\u00f3\u0142 Retta. W zwi\u0105zku z tym stworzyli\u015bmy model MDS \"MECP2 humanizado\", kt\u00f3ry zawiera dwa ludzkie bia\u0142ka MECP2 i \u017cadne szczurze bia\u0142ko endogenne. Wewn\u0105trzm\u00f3zgowe wstrzykni\u0119cie MECP2-ASO skutecznie regulowa\u0142o niski poziom ekspresji MECP2 w m\u00f3zgu tych szczur\u00f3w. Ponadto MECP2-ASO z\u0142agodzi\u0142 kilka deficyt\u00f3w behawioralnych i przywr\u00f3ci\u0142 ekspresj\u0119 wybranych gen\u00f3w regulowanych przez MECP2 w spos\u00f3b zale\u017cny od dawki bez \u017cadnej toksyczno\u015bci. Podawanie MECP2-ASO w o\u015brodkowym uk\u0142adzie nerwowym jest zatem dobrze tolerowane i korzystne w tym modelu szczur\u00f3w, co stanowi praktyczn\u0105 metod\u0119 leczenia MDS.<\/p>\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\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-background wp-element-button\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33658357\/\" style=\"border-radius:14px;background-color:#f7a13f\" target=\"_blank\" rel=\"noreferrer noopener\">Ver la publicaci\u00f3n<\/a><\/div>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Shao et al. del grupo del Prof. Zoghbi (Baylor College of Medicine, Texas, EE.UU.) publicaron un art\u00edculo en Science Translational medicine titulado \u00a0\u00bb Terapia con oligonucle\u00f3tidos antisentido en un modelo [&hellip;]<\/p>","protected":false},"author":1,"featured_media":13608,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[113],"tags":[],"class_list":["post-15078","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publicacion"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.8 - 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