{"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":"odwrocenie-fenotypow-w-modelach-myszy-mecp2-przy-uzyciu-oligonukleotydow-antysensownych","status":"publish","type":"post","link":"https:\/\/dupmecp2.eu\/pl\/odwrocenie-fenotypow-w-modelach-myszy-mecp2-przy-uzyciu-oligonukleotydow-antysensownych\/","title":{"rendered":"\"Reversione dei fenotipi in modelli di topi MECP2 usando oligonucleotidi antisenso\"."},"content":{"rendered":"<p class=\"wp-block-paragraph\"><strong>Prof. Huda Zoghbi wraz z zespo\u0142em z Baylor College of Medicine w Teksasie (USA) opublikowa\u0142a artyku\u0142 zatytu\u0142owany \u201eOdwracalno\u015b\u0107 fenotypu u myszy przy u\u017cyciu ratowania genetycznego lub oligonukleotyd\u00f3w antysensownych\u201d. Artyku\u0142 ten przedstawia wyniki zastosowania oligonukleotyd\u00f3w antysensownych w korygowaniu poziom\u00f3w MeCP2 oraz wywo\u0142ywaniu odwr\u00f3cenia zaburze\u0144 behawioralnych, molekularnych i elektrofizjologicznych w modelach zwierz\u0119cych z zespo\u0142em duplikacji MECP2.<\/strong><\/p>\n\n<p class=\"wp-block-paragraph\">Odwr\u00f3cenie fenotyp\u00f3w u myszy z duplikacj\u0105 MECP2 za pomoc\u0105 ratunku genetycznego lub oligonukleotyd\u00f3w antysensownych, Huda Zoghbi <em>i in,<\/em> <em>Natura<\/em><strong> 528, <\/strong>123-126 (2015)<\/p>\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n<p class=\"wp-block-paragraph\"><strong>RIASSUNTO DELL'ARTICOLO:<\/strong><\/p>\n\n<p class=\"wp-block-paragraph\">Zmiana liczby kopii genu jest cz\u0119sto wi\u0105zana z op\u00f3\u017anieniem rozwoju, niepe\u0142nosprawno\u015bci\u0105 intelektualn\u0105 oraz zaburzeniami ze spektrum autyzmu. Zesp\u00f3\u0142 duplikacji genu MECP2 jest jedn\u0105 z najcz\u0119stszych rearan\u017cacji genomowych u m\u0119\u017cczyzn i charakteryzuje si\u0119 autyzmem, niepe\u0142nosprawno\u015bci\u0105 intelektualn\u0105, zaburzeniami motorycznymi, l\u0119kiem, padaczk\u0105, cz\u0119stymi infekcjami dr\u00f3g oddechowych oraz przedwczesn\u0105 \u015bmierci\u0105.<\/p>\n\n<p class=\"wp-block-paragraph\">Szeroki zakres zaburze\u0144 spowodowanych nadmiern\u0105 produkcj\u0105 bia\u0142ka MECP2 stanowi du\u017ce wyzwanie dla tradycyjnych podej\u015b\u0107 terapeutycznych opartych na rozwa\u017caniach biochemicznych. W zwi\u0105zku z tym skupili\u015bmy si\u0119 na strategiach, kt\u00f3re bezpo\u015brednio celuj\u0105 w bia\u0142ko MeCP2 i kt\u00f3re mo\u017cna przenie\u015b\u0107 do praktyki klinicznej.<\/p>\n\n<p class=\"wp-block-paragraph\">Pierwszym pytaniem, na kt\u00f3re starali\u015bmy si\u0119 znale\u017a\u0107 odpowied\u017a, by\u0142o to, czy zaburzenia neurologiczne mog\u0105 by\u0107 odwracalne po pojawieniu si\u0119 objaw\u00f3w. Odwr\u00f3cenie fenotypu u doros\u0142ych myszy z objawami wykazano w modelach zaburze\u0144 neurologicznych spowodowanych monogenow\u0105 \u201eutrat\u0105 funkcji\u201d, w tym utrat\u0105 MeCP2 w zespole Retta. Wskazuje to, \u017ce przynajmniej w niekt\u00f3rych przypadkach neuroanatomia mo\u017ce pozosta\u0107 na tyle nienaruszona, \u017ce korekta dysfunkcji molekularnej le\u017c\u0105cej u podstaw tych zaburze\u0144 mo\u017ce przywr\u00f3ci\u0107 prawid\u0142owe funkcjonowanie organizmu.<\/p>\n\n<p class=\"wp-block-paragraph\">Bior\u0105c pod uwag\u0119 brak neurodegeneracji w zespole duplikacji genu MECP2, sugerujemy, \u017ce przywr\u00f3cenie prawid\u0142owego poziomu MeCP2 u doros\u0142ych myszy modelowych mo\u017ce skorygowa\u0107 ich fenotyp.<\/p>\n\n<p class=\"wp-block-paragraph\">Tworz\u0105c i charakteryzuj\u0105c model myszy z nadekspresj\u0105 bia\u0142ka MeCP2, wykazujemy, \u017ce korekta poziom\u00f3w MeCP2 w znacznym stopniu odwraca zaburzenia behawioralne, molekularne i elektrofizjologiczne.<\/p>\n\n<p class=\"wp-block-paragraph\">Poziomy MeCP2 zosta\u0142y obni\u017cone za pomoc\u0105 oligonukleotydu antysensownego.<\/p>\n\n<p class=\"wp-block-paragraph\">Cz\u0105steczki te s\u0105 zmodyfikowanymi kwasami nukleinowymi, kt\u00f3re mog\u0105 selektywnie hybrydyzowa\u0107 z RNA pos\u0142a\u0144cielskim transkrybowanym przez dany gen, wyciszaj\u0105c go, i zosta\u0142y ju\u017c z powodzeniem zastosowane w r\u00f3\u017cnych modelach myszy.<\/p>\n\n<p class=\"wp-block-paragraph\">Odkryli\u015bmy, \u017ce terapia oligonukleotydami antysensownymi powoduje znaczne przywr\u00f3cenie fenotypu u doros\u0142ych myszy transgenicznych z objawami zespo\u0142u duplikacji genu MECP2 (MECP2-TG) oraz koryguje poziomy MeCP2 w kom\u00f3rkach limfoblastoidalnych pacjent\u00f3w cierpi\u0105cych na zesp\u00f3\u0142 duplikacji MECP2 w zale\u017cno\u015bci od podanej dawki oligonukleotydu.<\/p>\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n<p class=\"wp-block-paragraph\"><\/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\">Alla pubblicazione<\/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 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ 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