美國研究人員6月26日在英國《自然》雜志上報(bào)告說，他們?cè)趯?shí)驗(yàn)鼠體內(nèi)實(shí)現(xiàn)了通過“剪切”和“粘貼”基因來治療血友病,。這一技術(shù)有望用于治療其他遺傳病,。
英國《自然》雜志網(wǎng)站刊登報(bào)告說，美國費(fèi)城兒童醫(yī)院等機(jī)構(gòu)的研究人員用這種方法有效治療了患有血友病的實(shí)驗(yàn)鼠,。血友病是由基因變異引起的一種遺傳病,，患者血液中缺少凝血物質(zhì)，往往有個(gè)小傷口就會(huì)流血不止,，通常只能采取注射凝血物質(zhì)的方法來進(jìn)行治療,。本次研究中的實(shí)驗(yàn)鼠患有乙型血友病，是由基因變異導(dǎo)致肝臟細(xì)胞不能產(chǎn)生一種凝血物質(zhì)引起,。
研究人員用病毒作為載體,，將一種名為“鋅指核酸酶”的物質(zhì)送入活體實(shí)驗(yàn)鼠的肝臟細(xì)胞中。鋅指核酸酶是基因?qū)W中所用的“剪刀”，可用于剪斷DNA（脫氧核糖核酸）鏈條,，研究人員用它精確地剪除了細(xì)胞DNA中基因序列上發(fā)生變異的部分,。隨后，再用病毒作為載體,，將一段正確的基因序列送入細(xì)胞中,，細(xì)胞在修復(fù)DNA鏈條的同時(shí)也就“粘貼”好了正確的基因序列。
結(jié)果顯示,，用這種方法治療的實(shí)驗(yàn)鼠,，體內(nèi)相應(yīng)凝血物質(zhì)的量可恢復(fù)到正常數(shù)量的5%左右，其血液也能較快自行凝結(jié),。領(lǐng)導(dǎo)研究的凱瑟琳·海伊說,，在相應(yīng)凝血物質(zhì)的量恢復(fù)到5%的情況下，血友病癥狀已大大減輕,，如果不是動(dòng)手術(shù)等情況,，一般不會(huì)出現(xiàn)嚴(yán)重的出血不止現(xiàn)象。
此前研究人員只對(duì)試管中的細(xì)胞“剪貼”過基因,，這是首次成功在活體動(dòng)物體內(nèi)進(jìn)行類似操作,。經(jīng)過8個(gè)月的觀察，實(shí)驗(yàn)鼠肝臟未出現(xiàn)異常,。研究人員因此認(rèn)為,，本次成果原則上證明了基因“剪貼”療法的有效性，將來也許可用于治療多種遺傳疾病,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature doi:10.1038/nature10177
In vivo genome editing restores haemostasis in a mouse model of haemophilia
Hojun Li; Virginia Haurigot; Yannick Doyon; Tianjian Li; Sunnie Y. Wong; Anand S. Bhagwat; Nirav Malani; Xavier M. Anguela; Rajiv Sharma; Lacramiora Ivanciu; Samuel L. Murphy; Jonathan D. Finn; Fayaz R. Khazi; Shangzhen Zhou; David E. Paschon; Edward J. Rebar; Frederic D. Bushman; Philip D. Gregory; Michael C. Holmes; Katherine A. High
Editing of the human genome to correct disease-causing mutations is a promising approach for the treatment of genetic disorders. Genome editing improves on simple gene-replacement strategies by effecting in situ correction of a mutant gene, thus restoring normal gene function under the control of endogenous regulatory elements and reducing risks associated with random insertion into the genome. Gene-specific targeting has historically been limited to mouse embryonic stem cells. The development of zinc finger nucleases (ZFNs) has permitted efficient genome editing in transformed and primary cells that were previously thought to be intractable to such genetic manipulation1. In vitro, ZFNs have been shown to promote efficient genome editing via homology-directed repair by inducing a site-specific double-strand break (DSB) at a target locus2, 3, 4, but it is unclear whether ZFNs can induce DSBs and stimulate genome editing at a clinically meaningful level in vivo. Here we show that ZFNs are able to induce DSBs efficiently when delivered directly to mouse liver and that, when co-delivered with an appropriately designed gene-targeting vector, they can stimulate gene replacement through both homology-directed and homology-independent targeted gene insertion at the ZFN-specified locus. The level of gene targeting achieved was sufficient to correct the prolonged clotting times in a mouse model of haemophilia B, and remained persistent after induced liver regeneration. Thus, ZFN-driven gene correction can be achieved in vivo, raising the possibility of genome editing as a viable strategy for the treatment of genetic disease.
