Nature:重磅!我国学者首次证实来自三个人的DNA,胚胎可正常发育

2022-09-08 转化医学网 转化医学网

在“CRISPR婴儿”丑闻发生后,该小组将重点转移到在实验室收集更多的安全数据。

导读:2016年,当第一个使用混合三个人遗传物质的技术怀孕的婴儿出生时,科学家们担心该程序尚未得到研究以证明其安全。现在,中国的科学家已经在早期人类胚胎中对这项技术进行了首次的全面研究,并报告说,它似乎并没有影响它们的发育。

用三个人的遗传物质创造婴儿的技术旨在防止线粒体(为细胞提供能量的细胞器)有缺陷的母亲将细胞传递给她们的孩子。线粒体含有自己的DNA,儿童从母亲那里继承了所有的线粒体。“线粒体替代疗法是一个有争议的领域,”该研究的共同作者,中国妇产科医生商微说。“通过我们的研究,我们希望为该技术的发展奠定基础。”

9月6日发表在《Nature》杂志上的研究报告提供了更多关于的线粒体替代疗法的细节。

https://www.nature.com/articles/d41586-022-02792-8

01 主轴传输

商微团队和汤富酬团队研究了三种主要类型的线粒体替代疗法之一的安全性,即纺锤体转移,用于第一个创造的具有三个人遗传物质的婴儿,其于2016年在墨西哥出生。在这种方法中,来自具有线粒体缺陷的女性卵子的核DNA被转移到具有健康线粒体的捐赠卵子中,且其核DNA已被移除。然后将卵子与父亲的精子在试管中受精。由此产生的胚胎除了来自供体的线粒体基因外,还含有来自父母双方的基因。

作为研究的一部分,该团队将数十个接受纺锤体移植的人类胚胎与对照组胚胎进行了比较。两组胚胎在受精后被允许发育达一周。研究人员发现,两组中来自五天大的“囊胚”的细胞具有几乎相同的基因表达和转录水平,这表明纺锤体转移似乎不会影响早期胚胎发育。

纽约市哥伦比亚大学的干细胞生物学家DietrichEgli说:“这是第一项对通过纺锤体转移产生的人类胚胎进行如此全面比较的研究。这项工作因其高质量和提供的数据量而“独特精彩。”Egli补充道:“纺锤体移植的安全性是意料之中的,因为以前的动物研究和2016年出生的健康孩子直到现在才最终得到证明是安全的。”

02 线粒体疾病

大约每5000名儿童中就有1名出生时患有由线粒体DNA有害突变引起的疾病。这些有缺陷的基因会导致许多器官出现问题,包括心脏和大脑。Egli说:“到目前为止,线粒体替代疗法似乎是阻止这些基因遗传给后代的最有效方法。”

但中国杭州西湖大学的线粒体生物学家蒋敏表示,线粒体替代疗法的长期影响尚不清楚。根据目前的技术,母亲的少量线粒体DNA将会无意中携带到供体卵子中,通常占胚胎总线粒体的2%不到。商微表示,他们已经改进了技术,以保持这一水平“几乎检测不到”,但蒋敏警告说,“研究表明,随着细胞的发育,母体线粒体DNA的比例可能会增加,从而增加了后代患线粒体疾病的风险。”

“母体线粒体和细胞核已经共存了很长一段时间,所以细胞核可能更喜欢具有母体线粒体的细胞,”蒋敏补充说,“这两个细胞器之间的相互作用需要更多的研究。到目前为止,研究表明主轴转移是有效的。但是使用该疗法出生的儿童的长期健康状况将需要通过临床试验进行调查。”

03 高度监管

目前只有少数国家,包括英国和澳大利亚,已经批准了线粒体替代疗法。商微表示,在“CRISPR婴儿”丑闻发生后,该小组将重点转移到在实验室收集更多的安全数据。

Egli表示,主轴转移的安全性研究将为不允许对该过程对其安全性和有效性进行评估的国家的监管机构提供重要证据。他说:“这真的有助于推动这个领域的发展。”

参考资料:

https://www.nature.com/articles/d41586-022-02792-8

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    2023-04-27 liye789132251
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    2022-09-09 ailian1202
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    2022-09-09 xxxx1054

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尽管DNA双螺旋结构被大家熟知,但是人类基因组的物理结构远比双螺旋复杂:总长近2米的DNA长链,在组蛋白,以及cohesin和CTCF等蛋白的帮助下被一步步压缩,包装成染色体结构,进而能被细胞核容纳。在这个过程中,DNA一维结构中相距较远的区域可能通过染色质环状结构(chromatin looping)在三维结构中反而比较接近,从而达到增强子远程调控的作用。但是这个包装过程的关键细节在很大程度上还

Nature:人造胚胎生成完整大脑及心脏

如果这些方法在未来被证明对人类干细胞是成功的,它们也可以用来指导等待移植的患者的合成器官的发育。

Nature:什么遗传因素会影响儿童的营养状态和发育成长?

人类全基因组关联研究(GWAS)已经确定了MC3R附近的常见变体,这些变体与成年身高和初潮年龄都有关联。

JNNP:一项发育障碍——C9orf72突变基因携带者的口语流利性不足

C9orf72中基因的突变使得肌萎缩性侧索硬化症(ALS)和额颞痴呆(FTD)之间发生了交联。在临床表现上,两种疾病都有可能表现出行为,语言障碍(FTD中)或运动功能障碍(在ALS中)。