英國(guó)研究人員14日說，他們?cè)谑澜缟鲜状闻嘤鰮碛幸粋€(gè)男性和兩個(gè)女性遺傳物質(zhì)的受精卵,，這一研究將來或許可以使母親避免把有缺陷的線粒體遺傳物質(zhì)遺傳給下一代,。但也有人擔(dān)心,，這一研究存在倫理問題。
英國(guó)紐卡斯?fàn)柎髮W(xué)研究人員在當(dāng)天的Nature雜志網(wǎng)絡(luò)版上報(bào)告說,，他們首次實(shí)現(xiàn)人類受精卵之間的DNA（脫氧核糖核酸）移植,，從而獲得一個(gè)擁有3個(gè)人遺傳物質(zhì)的受精卵，其中包括一名男性和一名女性的細(xì)胞核DNA,，以及另一名女性的線粒體DNA,。
負(fù)責(zé)這項(xiàng)研究的道格拉斯·特恩布爾教授說：“我們?cè)谠瓌t上證明：可以用相關(guān)技術(shù)來防止由線粒體引起的人類遺傳疾病。”
研究人員強(qiáng)調(diào)指出,，他們持有英國(guó)人工授精與胚胎學(xué)管理局頒發(fā)的執(zhí)照并遵守了相關(guān)規(guī)定,，沒有違反人類胚胎研究的道德規(guī)范。
線粒體在人類細(xì)胞中的作用是提供能量,，它所含有的遺傳物質(zhì)線粒體DNA只通過母系遺傳，即只來源于卵細(xì)胞,，與精子無關(guān),。由于未發(fā)生遺傳交換，母親的線粒體異常會(huì)導(dǎo)致許多遺傳疾病,，如Ⅱ型糖尿病等,。據(jù)統(tǒng)計(jì)，大約每200個(gè)新生兒中就有1個(gè)帶有可能致病的線粒體DNA變異,。
在本次研究中,，研究人員先從一對(duì)夫婦捐贈(zèng)的受精卵中取出細(xì)胞核，然后將其植入另一個(gè)去除了細(xì)胞核的受精卵中,。這個(gè)過程中幾乎沒有帶入線粒體DNA,，所獲得的受精卵因此含有原父母的細(xì)胞核DNA和另一名女性的線粒體DNA。這個(gè)新的受精卵被培育了6到8天至胚泡階段,，這證實(shí)它可以正常發(fā)育,。6到8天也是人工授精與胚胎學(xué)管理局規(guī)定的研究期限。
特恩布爾說,，這種技術(shù)可以避免有缺陷的線粒體DNA遺傳給下一代,。他說：“這就像為筆記本電腦更換電池,，硬盤上儲(chǔ)存的信息不會(huì)發(fā)生改變。”
不過也有專家認(rèn)為,，不同來源的細(xì)胞核DNA和線粒體DNA不一定總是相容,，存在產(chǎn)生沖突的風(fēng)險(xiǎn)。同時(shí),，由于存在倫理方面的爭(zhēng)議,，各國(guó)在法律上對(duì)類似研究都有一定限制，如英國(guó)目前不允許在人類子宮中培育使用上述方式產(chǎn)生的胚胎,。（生物谷Bioon.com）
延伸閱讀：
日本開發(fā)出甄別受精卵新技術(shù)
Nature：利用DNA核移植避免線粒體遺傳疾病
JCI：胰島細(xì)胞移植早期排斥反應(yīng)可控
生物谷推薦原文出處：
Nature 14 April 2010 doi:10.1038
Therapeutic antibody targeting of individual Notch receptors
Yan Wu1,9, Carol Cain-Hom2,9, Lisa Choy2, Thijs J. Hagenbeek2, Gladys P. de Leon7, Yongmei Chen1, David Finkle4, Rayna Venook4, Xiumin Wu5, John Ridgway5, Dorreyah Schahin-Reed6, Graham J. Dow2,10, Amy Shelton2, Scott Stawicki1, Ryan J. Watts6, Jeff Zhang8, Robert Choy8, Peter Howard8, Lisa Kadyk8, Minhong Yan5, Jiping Zha3, Christopher A. Callahan3, Sarah G. Hymowitz7 & Christian W. Siebel2
Top of pageAbstractThe four receptors of the Notch family are widely expressed transmembrane proteins that function as key conduits through which mammalian cells communicate to regulate cell fate and growth1, 2. Ligand binding triggers a conformational change in the receptor negative regulatory region (NRR) that enables ADAM protease cleavage3, 4 at a juxtamembrane site that otherwise lies buried within the quiescent NRR5, 6. Subsequent intramembrane proteolysis catalysed by the γ-secretase complex liberates the intracellular domain (ICD) to initiate the downstream Notch transcriptional program. Aberrant signalling through each receptor has been linked to numerous diseases, particularly cancer7, making the Notch pathway a compelling target for new drugs. Although γ-secretase inhibitors (GSIs) have progressed into the clinic8, GSIs fail to distinguish individual Notch receptors, inhibit other signalling pathways9 and cause intestinal toxicity10, attributed to dual inhibition of Notch1 and 2 (ref. 11). To elucidate the discrete functions of Notch1 and Notch2 and develop clinically relevant inhibitors that reduce intestinal toxicity, we used phage display technology to generate highly specialized antibodies that specifically antagonize each receptor paralogue and yet cross-react with the human and mouse sequences, enabling the discrimination of Notch1 versus Notch2 function in human patients and rodent models. Our co-crystal structure shows that the inhibitory mechanism relies on stabilizing NRR quiescence. Selective blocking of Notch1 inhibits tumour growth in pre-clinical models through two mechanisms: inhibition of cancer cell growth and deregulation of angiogenesis. Whereas inhibition of Notch1 plus Notch2 causes severe intestinal toxicity, inhibition of either receptor alone reduces or avoids this effect, demonstrating a clear advantage over pan-Notch inhibitors. Our studies emphasize the value of paralogue-specific antagonists in dissecting the contributions of distinct Notch receptors to differentiation and disease and reveal the therapeutic promise in targeting Notch1 and Notch2 independently.
