{"id":10668,"date":"2021-07-26T15:34:04","date_gmt":"2021-07-26T12:34:04","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=10668"},"modified":"2021-07-26T15:34:06","modified_gmt":"2021-07-26T12:34:06","slug":"crispr-ile-in-vivo-gen-editleme-heyecanlandirici-bir-ornek","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/crispr-ile-in-vivo-gen-editleme-heyecanlandirici-bir-ornek\/","title":{"rendered":"CRISPR \u0130LE IN VIVO GEN ED\u0130TLEME: HEYECANLANDIRICI B\u0130R \u00d6RNEK!"},"content":{"rendered":"\n

Ge\u00e7ti\u011fimiz ay yay\u0131nlanm\u0131\u015f bir makalede payla\u015f\u0131lan \u00e7al\u0131\u015fma sonu\u00e7lar\u0131na g\u00f6re, son zamanlarda geneti\u011fin en ilgi \u00e7ekici geli\u015fmelerinden olan CRISPR-Cas9 y\u00f6nteminin in vivo olarak kullan\u0131m\u0131 belgelenmi\u015ftir. Bu y\u00f6ntemin kullan\u0131m\u0131, \u201ctransthyretin amyloidosis<\/em>\u201d adl\u0131 hastal\u0131\u011f\u0131n gidi\u015fat\u0131na engel olabilen bir tedavi olarak uygulanm\u0131\u015f ve y\u00f6ntemin haberleri ger\u00e7ekten heyecan verici olmu\u015ftur. Bu ayki yaz\u0131mda hem bu uygulama ve yap\u0131lan ara\u015ft\u0131rma hakk\u0131nda hem de b\u00f6yle \u00f6nemli bir geli\u015fmenin, transthyretin amyloidosis gibi hastal\u0131klar\u0131n tedavisinin gelece\u011fi hakk\u0131nda ne ifade edebilece\u011fine dair bilgi vermeyi hedefliyorum.\u00a0<\/p>\n\n\n\n

\"\"
(http:\/\/amyloidosis.org\/wp-content\/uploads\/2017\/05\/2017-ATTR-guide.pdf)\u00a0<\/figcaption><\/figure>\n\n\n\n

TRANSTHYRET\u0130N AMYLO\u0130DOS\u0130S NED\u0130R? <\/strong><\/p>\n\n\n\n

\u201cTransthyretin amyloidosis\u201d\u00a0<\/em>(veya ATTR amyloidosis), \u00f6zellikle sinir ve kalp dokusunda TTR proteininin birikimiyle karakterize bir hastal\u0131kt\u0131r.\u00a0<\/strong>Bu hastal\u0131k hem kal\u0131tsal olarak hem de sonradan geli\u015ftirilerek g\u00f6zlemlenebilmektedir. Genelde ilerleme s\u00fcreci h\u0131zl\u0131 ve te\u015fhis konan ki\u015filerde\u00a0y\u00fcksek riskli\u00a0olan bir hastal\u0131k olarak de\u011ferlendirilmektedir. ATTR amyloidosis i\u00e7in genel olarak uygulanmakta olan tedaviler, hastalarda yanl\u0131\u015f bir bi\u00e7imde sentezlenen TTR proteininin olu\u015fturdu\u011fu amiloid birikimini azaltmaya veya bu protein sentezini engellemeye y\u00f6neliktir (Gillmore vd., 2021). Ancak bu tedavilerin hastalar\u0131n hayat kalitesini art\u0131rma anlam\u0131ndaki kabiliyetleri maalesef k\u0131s\u0131tl\u0131 kalabilmektedir. Makale yazarlar\u0131n\u0131n da belirtti\u011fi gibi, CRISPR\u2019\u0131n \u00e7ekici \u00f6zelli\u011fi genomda herhangi bir yerdeki genlerin bu mekanizmayla de\u011fi\u015ftirilebilece\u011fidir\u00a0(Kuchler, 2021)\u00a0ve bu hastal\u0131k monogenetik oldu\u011fu i\u00e7in de CRISPR-Cas9 endon\u00fckleaz sistemleriyle tedavi uygulamas\u0131 i\u00e7in iyi bir hedeftir. TTR proteininin yoklu\u011funda ya\u015fan\u0131labilece\u011fi d\u00fc\u015f\u00fcn\u00fclen fizyopatolojik durumlar\u0131n s\u0131n\u0131rl\u0131 olmas\u0131 da hastal\u0131\u011fa gen tedavisiyle \u00e7\u00f6z\u00fcm bulunabilece\u011fi d\u00fc\u015f\u00fcncesini desteklemektedir\u00a0(Gillmore vd., 2021).<\/p>\n\n\n\n

YAPILAN \u00c7ALI\u015eMA <\/strong><\/p>\n\n\n\n

Gillmore vd. taraf\u0131ndan y\u00fcr\u00fct\u00fclen ara\u015ft\u0131rma, NTLA-2001 ad\u0131 verilen ve intraven\u00f6z olarak uygulanan bir CRISPR-Cas9 sistemine dayanmaktad\u0131r. Bu gen terapisinin amac\u0131, karaci\u011fer h\u00fccrelerindeki TTR genini de\u011fi\u015ftirerek bu proteinin hem sa\u011fl\u0131kl\u0131 hem de mutasyona u\u011fram\u0131\u015f olarak sentezlenmesini engellemektir. Bu uygulama s\u00fcreci, Nobel \u00f6d\u00fcll\u00fc ara\u015ft\u0131rmac\u0131 Jennifer Doudna\u2019n\u0131n kurucular\u0131 aras\u0131nda yer ald\u0131\u011f\u0131 \u2018Intellia Therapeutics\u2019 adl\u0131 bir \u015firketten destek al\u0131narak y\u00fcr\u00fct\u00fclm\u00fc\u015f ve finanse edilmi\u015ftir (Kuchler, 2021). Ara\u015ft\u0131r\u0131lmakta olan gen tedavisi, hastalar\u0131n geninde de\u011fi\u015fim yapacak mekanizman\u0131n lipid nanopartik\u00fclleri vas\u0131tas\u0131yla karaci\u011fere iletilmesine dayanmaktad\u0131r (Yirka, 2021).  ATTR amyloidosis hastalar\u0131nda birikimi ger\u00e7ekle\u015fen proteinin \u00fcretimi neredeyse tamamen karaci\u011ferde ger\u00e7ekle\u015fti\u011fi i\u00e7in de nanopartik\u00fcllerin bu organ\u0131 hedefli bir \u015fekilde yap\u0131land\u0131r\u0131lm\u0131\u015f olmas\u0131n\u0131n faydal\u0131 olaca\u011f\u0131 d\u00fc\u015f\u00fcn\u00fclm\u00fc\u015ft\u00fcr. Ayn\u0131 zamanda bu \u015fekilde spesifik bir terapi uygulanabilece\u011fi, yan etkilerin azalt\u0131labilece\u011fi tahmin edilmi\u015ftir.<\/p>\n\n\n\n

Makalede sunulan sonu\u00e7lar, bu ilac\u0131n faz 1 s\u00fcrecine aittir. Gerekli \u00f6n \u00e7al\u0131\u015fmalar\u0131n tamamlanmas\u0131ndan sonra ilac\u0131n belirli gruplarda testi ba\u015flat\u0131lm\u0131\u015ft\u0131r. Hastalar, iki ila\u00e7 dozu grubu halinde takip edilmi\u015ftir. Rapora g\u00f6re, \u00e7al\u0131\u015fmaya kat\u0131lan ki\u015filere v\u00fccut a\u011f\u0131rl\u0131\u011f\u0131ndaki her kilogram i\u00e7in ya 0.1 mg ya da 0.3 mg RNA dozu verilmi\u015ftir. 28. g\u00fcnde kaydedilen verilere g\u00f6re TTR proteini seviyesindeki de\u011fi\u015fim 0.1 mg grubu i\u00e7in %52, 0.3 mg grubu i\u00e7in ise ortalama %87 olmu\u015ftur\u00a0(George, 2021). Dolay\u0131s\u0131yla \u015fu a\u015famada g\u00f6zlemlenen durum, ila\u00e7 etkisinin doza ba\u011fl\u0131 oldu\u011fu ve 0.3 mg doz grubunda etkinin daha y\u00fcksek oldu\u011fu y\u00f6n\u00fcndedir. Tedavinin uyguland\u0131\u011f\u0131 ki\u015filerde NTLA-2001\u2019e g\u00f6sterilen\u00a0yan tesirlerin\u00a0de olabildi\u011fince az oldu\u011fu kaydedilmi\u015ftir.\u00a0<\/p>\n\n\n\n

NTLA-2001 ve \u00fczerine yap\u0131lan ara\u015ft\u0131rma, hem CRISPR tekni\u011finin \u015fimdiye kadar oldu\u011fundan daha geni\u015f \u00e7apl\u0131 kullan\u0131m\u0131 hem de bu tekni\u011fin \u00e7e\u015fitli hastal\u0131klar i\u00e7in geli\u015ftirilebilmesi i\u00e7in \u00f6nemli ve heyecan verici bir ad\u0131md\u0131r. Bahsi ge\u00e7en \u00e7al\u0131\u015fma halen devam etmektedir. G\u00fcn\u00fcm\u00fczde ATTR amyloidosis hastalar\u0131n\u0131n kullanabildi\u011fi tedavilerden daha kal\u0131c\u0131 bir tedavi yakla\u015f\u0131m\u0131na ula\u015fmak, TTR protein birikimini (ve dolay\u0131s\u0131yla hastal\u0131\u011f\u0131n ilerlemesini) olabildi\u011fince azaltmak ve hastalar\u0131n hayat kalitelerini art\u0131rmak ama\u00e7lanmaktad\u0131r. Bilim insanlar\u0131, bu ilac\u0131 daha detayl\u0131 ara\u015ft\u0131rmay\u0131 ve sonraki ad\u0131mlar\u0131n getirdi\u011fi sonu\u00e7lara g\u00f6re daha geni\u015f hasta kitlelerinde de bunu denemeyi planlamaktad\u0131r (Yirka, 2021).\u00a0<\/p>\n\n\n\n

Not: E\u011fer bahsi ge\u00e7en \u00e7al\u0131\u015fma hakk\u0131nda daha detayl\u0131 bilgi almak isterseniz bu linkten makaleye ula\u015fabilirsiniz:\u00a0https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa2107454<\/a>.\u00a0\u00a0<\/p>\n\n\n\n

KAYNAK\u00c7A<\/strong><\/p>\n\n\n\n

George, J. (2021, Haziran 28).\u00a0In a First, CRISPR Infusion Edits Genes Directly in Humans<\/em>. MedPage Today. https:\/\/www.medpagetoday.com\/neurology\/generalneurology\/93314<\/p>\n\n\n\n

Gillmore, J. D., Gane, E., Taubel, J., Kao, J., Fontana, M., Maitland, M. L., Seitzer, J., O\u2019Connell, D., Walsh, K. R., Wood, K., Phillips, J., Xu, Y., Amaral, A., Boyd, A. P., Cehelsky, J. E., McKee, M. D., Schiermeier, A., Harari, O., Murphy, A., \u2026 Lebwohl, D. (2021). CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis.\u00a0New England Journal of Medicine<\/em>,\u00a00<\/em>(0), null. https:\/\/doi.org\/10.1056\/NEJMoa2107454<\/p>\n\n\n\n

Kuchler, H. (2021, Haziran 27). Crispr gene-editing \u2018revolution\u2019 treats internal organ for first time.\u00a0Financial Times<\/em>. https:\/\/www.ft.com\/content\/ccc4132a-9a4b-4c06-ad2c-a45af3deeb2e<\/p>\n\n\n\n

Yirka, B. (2021, Haziran 28).\u00a0First clinical trial involving in vivo CRISPR human gene editing<\/em>. Medical Express. https:\/\/medicalxpress.com\/news\/2021-06-clinical-trial-involving-vivo-crispr.html<\/p>\n","protected":false},"excerpt":{"rendered":"

Ge\u00e7ti\u011fimiz ay yay\u0131nlanm\u0131\u015f bir makalede payla\u015f\u0131lan \u00e7al\u0131\u015fma sonu\u00e7lar\u0131na g\u00f6re, son zamanlarda geneti\u011fin en ilgi \u00e7ekici geli\u015fmelerinden olan CRISPR-Cas9 y\u00f6nteminin in<\/p>\n","protected":false},"author":273,"featured_media":10670,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[],"acf":[],"views":630,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/10668"}],"collection":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/users\/273"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=10668"}],"version-history":[{"count":2,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/10668\/revisions"}],"predecessor-version":[{"id":10672,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/10668\/revisions\/10672"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/10670"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=10668"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=10668"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=10668"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}