Um\u011bl\u00e9 z\u00e1sahy do genetick\u00e9ho k\u00f3du b\u00fdvaj\u00ed obl\u00edben\u00fdm n\u00e1m\u011btem mnoha sci-fi knih a filmov\u00fdch sc\u00e9n\u00e1\u0159\u016f. V\u00a0nov\u00e9m tis\u00edcilet\u00ed se science fiction stalo realitou. P\u0159edm\u011btem z\u00e1jmu v\u011bdeck\u00fdch t\u00fdm\u016f v\u0161ak nejsou mutanti \u010di k\u0159\u00ed\u017eenci lid\u00ed a zv\u00ed\u0159at. Jejich c\u00edl lze popsat dv\u011bma slovy: genov\u00e1 terapie.<\/p>\n
V sou\u010dasn\u00e9 dob\u011b je pops\u00e1no v\u00edce ne\u017e 75 000 genetick\u00fdch variant, kter\u00e9 souvisej\u00ed s lidsk\u00fdmi onemocn\u011bn\u00edmi. Choroby vznikaj\u00ed, pokud dojde k naru\u0161en\u00ed funkce gen\u016f. Po\u0161kozen\u00ed genu m\u016f\u017ee b\u00fdt r\u016fzn\u011b velk\u00e9. Geny se skl\u00e1daj\u00ed ze sekvence stovek a\u017e tis\u00edc\u016f nukleotid\u016f (p\u00edsmen A, C, G, T), kter\u00e9 maj\u00ed p\u0159esn\u011b definovan\u00e9 po\u0159ad\u00ed. U n\u011bkter\u00fdch gen\u016f sta\u010d\u00ed z\u00e1m\u011bna \u010di absence jedin\u00e9ho nukleotidu (p\u00edsmene) k propuknut\u00ed z\u00e1va\u017en\u00e9ho onemocn\u011bn\u00ed. Genov\u00ed in\u017een\u00fd\u0159i se proto zam\u011b\u0159ili na v\u00fdvoj technik, kter\u00e9 by jim umo\u017enily defektn\u00ed geny opravit.<\/p>\n
Jak se uk\u00e1zalo, vlo\u017een\u00ed nov\u00e9ho funk\u010dn\u00edho genu do genomu nebylo t\u00edm nejslo\u017eit\u011bj\u0161\u00edm. Hlavn\u00edm probl\u00e9mem bylo, \u017ee v\u011bdci nem\u011bli kontrolu nad m\u00edstem, kam se nov\u00fd gen zabudoval. To znamenalo pot\u00ed\u017ee zejm\u00e9na v\u00a0p\u0159\u00edpad\u011b, \u017ee nov\u011b vlo\u017een\u00fd gen p\u0159eru\u0161il sekvenci jin\u00e9ho d\u016fle\u017eit\u00e9ho genu. Z\u00e1rove\u0148 nebyly zn\u00e1my techniky, jak vypnout p\u016fvodn\u00ed po\u0161kozen\u00fd gen.<\/p>\n
Za pr\u016flomov\u00fd objev je ozna\u010dov\u00e1n tzv. CRISPR-Cas9. Jedn\u00e1 se o kombinaci enzymu CRISPR, kter\u00fd umo\u017e\u0148uje rozst\u0159i\u017een\u00ed dvou\u0161roubovice DNA v\u00a0po\u017eadovan\u00e9m m\u00edst\u011b. Genov\u00ed in\u017een\u00fd\u0159i vych\u00e1zeli z\u00a0poznatku, \u017ee si lidsk\u00e9 bu\u0148ky evolu\u010dn\u011b vyvinuly opravn\u00e9 mechanismy na obnoven\u00ed po\u0161kozen\u00fdch sekvenc\u00ed genetick\u00e9ho k\u00f3du. Pokud tedy sou\u010dasn\u011b vlo\u017eili do bu\u0148ky i nov\u00fd genov\u00fd konstrukt (sekvenci p\u00edsmen), byla velk\u00e1 pravd\u011bpodobnost, \u017ee ho bu\u0148ka pou\u017eije k\u00a0oprav\u011b rozst\u0159i\u017een\u00e9ho m\u00edsta. T\u00edm se stane um\u011ble vlo\u017een\u00e1 sekvence sou\u010d\u00e1st\u00ed bu\u0148ky. V\u00a0roce 2015 \u010d\u00edn\u0161t\u00ed v\u011bdci jako prvn\u00ed publikovali v\u00fdsledky studie odhaluj\u00edc\u00ed \u00fasp\u011b\u0161nou v\u00fdm\u011bnu defektn\u00edch gen\u016f ne\u017eivotaschopn\u00fdch lidsk\u00fdch embry\u00ed. CRISPR-Cas9 se rychle roz\u0161\u00ed\u0159il do v\u0161ech p\u0159edn\u00edch sv\u011btov\u00fdch laborato\u0159\u00ed a stal se z\u00e1kladn\u00edm stavebn\u00edm kamenem pro\u00a0v\u00fdvoj nov\u00fdch technik genov\u00fdch terapi\u00ed.<\/p>\n
V\u00a0\u0159\u00edjnov\u00e9m \u010d\u00edsle presti\u017en\u00edho \u010dasopisu Nature p\u0159edstavil v\u00fdzkumn\u00fd t\u00fdm pod veden\u00edm Davida R. Liu (Broad Institute of MIT a Harvard Cambridge, Massachusetts) zcela novou technologii ozna\u010dovanou jako prime editing. Prime editing je precizn\u00ed metoda editace genomu, kter\u00e1 rovn\u011b\u017e vyu\u017e\u00edv\u00e1 enzymu Cas9 pro st\u0159ih DNA v\u00a0konkr\u00e9tn\u00edm m\u00edst\u011b. Z\u00e1kladn\u00ed rozd\u00edl oproti metod\u011b CRISPR-Cas9 tkv\u00ed v p\u0159eru\u0161en\u00ed jen jednoho vl\u00e1kna dvou\u0161roubovice DNA a p\u0159edlo\u017een\u00ed konkr\u00e9tn\u00edho n\u00e1vodu pro jeho opravu. T\u00edmto n\u00e1vodem je speci\u00e1ln\u00ed molekula pegRNA (prime editing guide RNA), podle kter\u00e9 bu\u0148ka oprav\u00ed po\u0161kozen\u00e9 vl\u00e1kno. Po p\u0159eru\u0161en\u00ed druh\u00e9ho vl\u00e1kna je pak podle nov\u011b vznikl\u00e9 sekvence opraveno i\u00a0vl\u00e1kno druh\u00e9. David R. Liu provedl se sv\u00fdmi kolegy ji\u017e v\u00edce ne\u017e 175 \u00faprav v lidsk\u00fdch bu\u0148k\u00e1ch, v\u010detn\u011b c\u00edlen\u00fdch inzerc\u00ed, delec\u00ed a v\u0161ech 12 typ\u016f bodov\u00fdch mutac\u00ed (z\u00e1m\u011bn p\u00edsmen). Prime editing p\u0159edstavuje bezpe\u010dn\u00fd n\u00e1stroj pro korekci velk\u00e9 v\u011bt\u0161iny patogenn\u00edch genetick\u00fdch variant. Hlavn\u00ed autor studie, David Liu, uvad\u00ed, \u017ee by prime editing mohl b\u00fdt \u00fa\u010dinnou genovou terapi\u00ed u t\u00e9m\u011b\u0159 90\u00a0% z\u00a0v\u00edce ne\u017e 75\u00a0000 variant DNA souvisej\u00edc\u00edch s\u00a0onemocn\u011bn\u00edm.<\/p>\n
Rozvoj genov\u00e9ho in\u017een\u00fdrstv\u00ed s\u00a0sebou p\u0159in\u00e1\u0161\u00ed i mnoho ot\u00e1zek t\u00fdkaj\u00edc\u00edch se z\u00e1kon\u016f a etiky. V\u00a0Evrop\u011b plat\u00ed tzv. Oviedsk\u00e1 deklarace, jej\u00ed\u017e \u010dl\u00e1nek 13 definuje \u00famluvy o lidsk\u00fdch pr\u00e1vech a\u00a0biomedic\u00edn\u011b. Z\u00e1sahy do genomu lze prov\u00e1d\u011bt pro preventivn\u00ed, diagnostick\u00e9 nebo l\u00e9\u010debn\u00e9 \u00fa\u010dely, pokud dan\u00e9 zm\u011bny nebudou p\u0159eneseny na potomstvo. Velk\u00fd rozruch vyvolal v\u00a0\u0159\u00edjnu roku 2018 \u010d\u00ednsk\u00fd v\u011bdec He Jiankui (\u00a0Southern University of Science and Technology in\u00a0Shenzhen, China), kter\u00fd vystoupil se sd\u011blen\u00edm, \u017ee provedl genetickou \u00fapravu embry\u00ed, ze kter\u00fdch se narodila dvoj\u010data Lulu a Nana. Pomoc\u00ed technologie CRISPR-Cas9 modifikoval v\u00a0embry\u00edch gen CCR5<\/em> s\u00a0c\u00edlem navodit genetickou rezistenci v\u016f\u010di viru HIV. Zm\u00edn\u011bn\u00e1 genov\u00e1 terapie by mohla umo\u017enit po\u010det\u00ed d\u011bt\u00ed i HIV pozitivn\u00edm rodi\u010d\u016fm. V\u011bt\u0161ina sv\u011btov\u00fdch v\u011bdeck\u00fdch spole\u010dnost\u00ed v\u0161ak experiment odsoudila z\u00a0etick\u00fdch d\u016fvod\u016f. Tento p\u0159\u00edpad ukazuje, jak je d\u016fle\u017eit\u00e9 v\u011bnovat pozornost i etick\u00fdm, pr\u00e1vn\u00edm a soci\u00e1ln\u00edm d\u016fsledk\u016fm\u00a0genetick\u00e9ho v\u00fdzkumu.<\/p>\n <\/p>\n Zdroj:<\/p>\n ANZALONE, Andrew V., Peyton B. RANDOLPH, Jessie R. DAVIS, et al. Search-and-replace genome editing without double-strand breaks or donor DNA.\u00a0Nature\u00a0[online]. 2019,\u00a0576(7785), 149-157 [cit. 2019-12-17]. DOI: 10.1038\/s41586-019-1711-4. ISSN 0028-0836. Dostupn\u00e9 z: http:\/\/www.nature.com\/articles\/s41586-019-1711-4<\/p>\n LEDFORD, Heidi. Super-precise new CRISPR tool could tackle a plethora of genetic diseases.\u00a0Nature\u00a0[online]. 2019,\u00a0574(7779), 464-465 [cit. 2019-12-17]. DOI: 10.1038\/d41586-019-03164-5. ISSN 0028-0836. Dostupn\u00e9 z: http:\/\/www.nature.com\/articles\/d41586-019-03164-5<\/p>\n","protected":false},"excerpt":{"rendered":" Um\u011bl\u00e9 z\u00e1sahy do genetick\u00e9ho k\u00f3du b\u00fdvaj\u00ed obl\u00edben\u00fdm n\u00e1m\u011btem mnoha sci-fi knih a filmov\u00fdch sc\u00e9n\u00e1\u0159\u016f. V\u00a0nov\u00e9m […]<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"image","meta":{"_uag_custom_page_level_css":""},"categories":[1],"tags":[],"uagb_featured_image_src":{"full":false,"thumbnail":false,"medium":false,"medium_large":false,"large":false,"1536x1536":false,"2048x2048":false,"boldthemes_grid":false,"boldthemes_grid_11":false,"boldthemes_grid_22":false,"boldthemes_grid_21":false,"boldthemes_grid_12":false,"boldthemes_latest_posts":false,"boldthemes_grid_gallery":false},"uagb_author_info":{"display_name":"Jbednar","author_link":"https:\/\/www.mc-praha.cz\/mcp\/author\/jbednar\/"},"uagb_comment_info":0,"uagb_excerpt":"Um\u011bl\u00e9 z\u00e1sahy do genetick\u00e9ho k\u00f3du b\u00fdvaj\u00ed obl\u00edben\u00fdm n\u00e1m\u011btem mnoha sci-fi knih a filmov\u00fdch sc\u00e9n\u00e1\u0159\u016f. V\u00a0nov\u00e9m […]","post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts\/3289"}],"collection":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/comments?post=3289"}],"version-history":[{"count":2,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts\/3289\/revisions"}],"predecessor-version":[{"id":3292,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts\/3289\/revisions\/3292"}],"wp:attachment":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/media?parent=3289"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/categories?post=3289"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/tags?post=3289"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}