利用DNA交換避免線粒體遺傳疾病的信息分析

據《自然》網站報道，線粒體DNA只會由母親傳給后代，因為精子中的線粒體并不向胚胎貢 獻DNA。線粒體DNA突變與許多疾病存在關聯，比如Ⅱ型糖尿病、線粒體肌病以及Leigh綜合癥（常見于嬰兒的神經退化性疾病）等。如今，一種在卵細胞 間轉移遺傳物質的新技術有望被用來預防由線粒體DNA突變導致的遺傳性疾病。

 

美國俄勒岡州國家靈長類動物研究中心的Shoukhrat Mitalipov及其小組以恒河猴為實驗對象，將一個卵細胞中的核DNA移入另一個去核卵細胞中，之后進行授精并植入子宮。這樣生下的后代將具有一個母體的線粒體DNA和另一個母體的核DNA。

 

共15個胚胎被植入9個代孕母體，3個成功懷孕，其中1個為雙胞胎，共產下4個后代。這與人類中的試管授精成功率相當。相關論文報告8月26日在線發表于《自然》雜志。該論文共報告了其中的3個后代，目前沒有發現異常狀況。

 

線粒體疾病研究界對此研究感到鼓舞。澳大利亞墨爾本默多克兒童研究所專攻線粒體疾病的遺 傳學家David Thorburn表示，該研究屏除了所有攜帶致病突變的線粒體DNA，而且是在靈長類動物中完成的，這使得該研究“具有高度的創新意義，非常有前途”，“ 它應該能夠比小鼠更近地模擬人類狀況，如果能在人體中證明安全，將是一個巨大的進步”。美國聯合線粒體疾病基金會科學與醫學顧問委員會成員、邁阿密大學細 胞生物學家Carlos Moraes說：“（這類）研究需要成本，也存在風險，但獲益大于弊端。”

1. Oregon National Primate Research Center,
2. Oregon Stem Cell Center and,
3. Departments of Obstetrics and Gynecology and Molecular and Medical Genetics, Oregon Health and Science University, 505 N.W. 185^th Avenue, Beaverton, Oregon 97006, USA

Correspondence to: Shoukhrat Mitalipov^1,2,3 Correspondence and requests for materials should be addressed to S.M. (Email: mitalipo@ohsu.edu).

 

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Abstract

Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin. Mutations in mtDNA contribute to a diverse range of currently incurable human diseases and disorders. To establish preclinical models for new therapeutic approaches, we demonstrate here that the mitochondrial genome can be efficiently replaced in mature non-human primate oocytes (Macaca mulatta) by spindle–chromosomal complex transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilization, embryo development and produced healthy offspring. Genetic analysis confirmed that nuclear DNA in the three infants born so far originated from the spindle donors whereas mtDNA came from the cytoplast donors. No contribution of spindle donor mtDNA was detected in offspring. Spindle replacement is shown here as an efficient protocol replacing the full complement of mitochondria in newly generated embryonic stem cell lines. This approach may offer a reproductive option to prevent mtDNA disease transmission in affected families.