【佳學(xué)基因檢測】CRISPR/dCas9 基因治療神經(jīng)發(fā)育障礙：與傳統(tǒng)策略相比的創(chuàng)新和局限性

靶向藥一般多少錢排名

研究高效抑制神經(jīng)系統(tǒng)合并癥的方法與藥物時(shí)看到《Dev Neurosci》在2021;43(3-4):253-261發(fā)表了一篇題目為《CRISPR/dCas9 作為神經(jīng)發(fā)育障礙的治療方法：與傳統(tǒng)策略相比的創(chuàng)新和局限性》神經(jīng)系統(tǒng)疾病的基因修飾治療的臨床研究文章。該研究由Raffaele Ricci, Gaia Colasante等完成。促進(jìn)了基因編輯技術(shù)等正確治療手段在神經(jīng)發(fā)育障礙領(lǐng)域的應(yīng)用，在基因檢測指導(dǎo)下的創(chuàng)新療法即有創(chuàng)新性也有一定的局限性，為基因解碼的進(jìn)一步發(fā)展提出了新的課題。

神經(jīng)疾病遺傳阻斷及正確治療臨床研究內(nèi)容關(guān)鍵詞：

CRISPR,dCas9,基因治療,神經(jīng)發(fā)育障礙,精神疾病,正確治療

精神類疾病用藥指導(dǎo)基因檢測臨床應(yīng)用結(jié)果

大腦發(fā)育是一個(gè)復(fù)雜的過程，需要一系列正確并相互協(xié)調(diào)的事件發(fā)生。當(dāng)基因檢測到的突變使得其中一些事件發(fā)生改變時(shí)，可能會(huì)出現(xiàn)神經(jīng)發(fā)育障礙 (NDD)，并出現(xiàn)其特征性癥狀，包括認(rèn)知、社交運(yùn)動(dòng)缺陷和癲癇。雖然多年來藥物治療一直是少有的治療選擇，但賊近的研究轉(zhuǎn)向直接消除每個(gè)特定神經(jīng)發(fā)育障礙的致病基因突變。這要?dú)w功于對(duì)這些疾病的基因解碼基礎(chǔ)知識(shí)的增加以及基因組編輯工具的巨大進(jìn)步。與基于聚集規(guī)則間隔短回文重復(fù) (CRISPR)/Cas9 的策略一起，核酸酶缺陷 Cas9 (dCas9) 工具也有了很大的發(fā)展，該工具具有極大的靈活性，允許將特定的蛋白質(zhì)功能募集到所需的基因組位點(diǎn)。在這項(xiàng)工作中，佳學(xué)基因解碼回顧了基于 dCas9 的工具，并討論了所有已發(fā)表的在臨床前水平的神經(jīng)發(fā)育障礙治療方法設(shè)置中的應(yīng)用。特別是針對(duì) Dravet 綜合征、C11orf46 基因突變引起的胼胝體連接障礙和脆性 X 綜合征的基于 dCas9 的治療策略進(jìn)行了介紹和討論。提供了與其他可能的治療策略的直接比較，例如經(jīng)典基因替換或基于 CRISPR/Cas9 的策略。佳學(xué)基因檢測不僅強(qiáng)調(diào)了與以前的策略相比具有明顯優(yōu)勢的那些方面，而且還強(qiáng)調(diào)了與其應(yīng)用相關(guān)的需要克服的主要技術(shù)障礙。關(guān)鍵詞：CRISPR/dCas9；基因治療;神經(jīng)發(fā)育障礙。

神經(jīng)及精神疾病及其并發(fā)征、合并征國際數(shù)據(jù)庫描述：

Brain development is a complex process that requires a series of precise and coordinated events to take place. When alterations in some of those events occur, neurodevelopmental disorders (NDDs) may appear, with their characteristic symptoms, including cognitive, social motor deficits, and epilepsy. While pharmacologic treatments have been the only therapeutic options for many years, more recently the research is turning to the direct removal of the underlying genetic cause of each specific NDD. This is possible thanks to the increased knowledge of genetic basis of those diseases and the enormous advances in genome-editing tools. Together with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based strategies, there is a great development also of nuclease defective Cas9 (dCas9) tools that, with an extreme flexibility, allow the recruitment of specific protein functions to the desired genomic sites. In this work, we review dCas9-based tools and discuss all the published applications in the setting of therapeutic approaches for NDDs at the preclinical level. In particular, dCas9-based therapeutic strategies for Dravet syndrome, transcallosal dysconnectivity caused by mutations in C11orf46 gene, and Fragile X syndrome are presented and discussed. A direct comparison with other possible therapeutic strategies, such as classic gene replacement or CRISPR/Cas9-based strategies, is provided. We also highlight not only those aspects that constitute a clear advantage compared to previous strategies but also the main technical hurdles related to their applications that need to be overcome.Keywords: CRISPR/dCas9; Gene therapy; Neurodevelopmental disorders.