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基因编辑技术一周之内实现两大进展

基因编辑技术一周之内实现两大进展

Sy Mukherjee 2017年11月01日
未来我们的培根和猪肉产品脂肪含量会更少。

本周,CRISPR基因编辑技术这个伟大的新领域有了两大重要进展。其中之一可能意味着令人忧伤或激动(这取决于你更偏向你的味蕾还是你的动脉)的前景:未来我们的培根和猪肉产品脂肪含量会更少。

不过先让我们抛开关于培根的新闻。没错,从技术上说,这个特殊的里程碑与培根没关系。实际上,它是关于提高新生猪崽和小猪崽的存活概率,让它们更容易抵御寒冷导致的休克(由于某个遗传问题,猪崽们不太抗寒)。位于北京的中国科学院大学(University of Chinese Academy of Sciences)的科学家利用了名为CRISPR Cas-9的基因编辑技术——本质上说,这是一种分子剪刀,可用于切割特定的DNA片段,并用其他基因序列取代它——来修复猪体内的解偶联蛋白-1(uncoupling protein 1, UCP1)基因。新基因可以更有效地将脂肪转化为能量和热量,科学家从老鼠的体内复制了它,并将其植入猪胚胎中。

结果呢?小猪崽的脂肪重量比降低了20%,不过它们在低温下可以更好地产生热量抵御寒冷。所以这实际上是个不错的做法——让容易因为冷休克而死亡的小猪崽有了更好的生命力。如果你担心未来的猪肉会太瘦,味道不那么可口,请记住:由基因改造的动物制成的食品,在美国是一个争议很大的话题,食品和药物监督管理局(Food and Drug Administration, FDA)花了几十年时间,才终于在2015年给第一只基因改造的动物开了绿灯。

我们可以据此引申到第二个进展,它可能会对未来的科学和医疗造成更加深远的影响。Cas9只是一种可以用于CRISPR基因编辑过程的酶,此外,还有其他实现CRISPR基因改造的办法——其中一种被称作“碱基编辑”(base editing)。在本周三的《自然》(Nature)和《科学》(Science)杂志上,哈佛-麻省理工大学Broad研究所(Broad Institute of MIT and Harvard)的研究人员对其进行了介绍。

如《麻省理工科技评论》(MIT Technology Review)所言,该系统几乎可以被看作是CRISPR 2.0。科学家能够把已有DNA的单个组成部分(人类基因组的碱基对是A-T和C-G,这四种分子结构单元构成了生命,决定了我们从外表到毁灭性疾病在内的一切特质)改成另一个。他们可以把“A”(代表腺嘌呤)改成某种类似“G”(鸟嘌呤)的物质。

这种化学上的取代会产生什么样的结果呢?与被替代的“A”配对的“T”(胸腺嘧啶)也会变化,所以整个碱基对就变成了胞嘧啶-鸟嘌呤(C-G)。与CRISPR相比,这是个完全不同的里程碑。该技术更像是分子层面的剪刀,来切割和取代整个碱基对。这类碱基编辑工具可以针对非常精确的个体,或“点”,这些地方的突变是许多遗传疾病发生的根本原因。(财富中文网)

译者:严匡正

There’s been a one-two punch of significant developments in the brave new world of CRISPR gene editing this week—and one of them potentially includes the saddening/encouraging prospect of less fatty bacon and pork products sometime in the future (depending on whether you’re deferring to your taste buds or your arteries, respectively).

Let’s get the bacon-centric news out of the way first. All right, so technically, this particular milestone isn’t about bacon. In fact, it’s about giving newborn and young piglets a better chance of surviving by making it easier for them to withstand shock from cold (something they are not particularly good at doing because of a genetic quirk). Scientists at the University of Chinese Academy of Sciences in Beijing were able to leverage the gene editing technique known as CRISPR Cas-9—in essence, molecular shears that can be targeted to slice and dice certain DNA segments and let them be replaced by other genetic sequences—to restore a gene called uncoupling protein 1 (UCP1) in pigs. This gene, which allows for a more efficient way to turn fat into energy and heat, was replicated from mice and put into pig embryos.

The result? Piglets with a 20 percent lower fat to weight ratio and a better ability to generate heat in cold temperatures. So it’s actually for a good cause—giving piglets, which have a higher tendency of dying from cold shock, a better shot at life. And if you’re worried about a future filled with skinny, less scrumptious pork segments, just remember: Food from engineered animals is such a controversial topic in America that it literally took the Food and Drug Administration (FDA) decades before approving the first genetically modified animal in 2015.

That brings us to the second development, which could have significantly more far-reaching scientific and medical repercussions down the line. Cas9 is just one type of enzyme that can be used in the CRISPR gene-editing process; but there are other ways to approach CRISPR gene modification—including one called “base editing” that’s described in two papers published in Nature and Science by researchers from the Broad Institute of MIT and Harvard on Wednesday.

As the MIT Technology Review notes, this system could almost be thought of as CRISPR 2.0. The scientists were able to actually change existing, individual DNA components (the base pairs of the human genome are A-T and C-G, representing the four molecular building blocks which make up life and determine everything from how we look to whether we carry certain devastating illnesses) into other ones. They transformed an “A” (which stands for adenine) into something that resembled a “G” (or guanine).

The net result of this chemical impostor’s presence? The original “T” (or thymine) paired with the now-transformed “A” also changed so that the molecular pair transformed into a cytosine-guanine (C-G) base pair. That’s a very different kind of milestone compared to CRISPR, which is more of a molecular set of shears to cut out and replace entire base pairs. Instead, this kind of base editing tool could be used to very precisely target individual, or “point,” mutations at the root of many genetic diseases.

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