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基因編輯技術一周之內實現兩大進展

2017-12-23


本周,CRISPR基因編輯技術這個偉大的新領域有了兩大重要進展。其中之一可能意味著令人憂傷或激動(這取決于你更偏向你的味蕾還是你的動脈)的前景:未來我們的培根和豬肉產品脂肪含量會更少。

不過先讓我們拋開關于培根的新聞。沒錯,從技術上說,這個特殊的里程碑與培根沒關系。實際上,它是關于提高新生豬崽和小豬崽的存活概率,讓它們更容易抵御寒冷導致的休克(由于某個遺傳問題,豬崽們不太抗寒)。位于北京的中國科學院大學(University of Chinese Academy of Sciences)的科學家利用了名為CRISPR Cas-9的基因編輯技術——本質上說,這是一種分子剪刀,可用于切割特定的DNA片段,并用其他基因序列取代它——來修復豬體內的解偶聯蛋白-1(uncoupling protein 1, UCP1)基因。新基因可以更有效地將脂肪轉化為能量和熱量,科學家從老鼠的體內復制了它,并將其植入豬胚胎中。

結果呢?小豬崽的脂肪重量比降低了20%,不過它們在低溫下可以更好地產生熱量抵御寒冷。所以這實際上是個不錯的做法——讓容易因為冷休克而死亡的小豬崽有了更好的生命力。如果你擔心未來的豬肉會太瘦,味道不那么可口,請記住:由基因改造的動物制成的食品,在美國是一個爭議很大的話題,食品和藥物監督管理局(Food and Drug Administration, FDA)花了幾十年時間,才終于在2015年給第一只基因改造的動物開了綠燈。

我們可以據此引申到第二個進展,它可能會對未來的科學和醫療造成更加深遠的影響。Cas9只是一種可以用于CRISPR基因編輯過程的酶,此外,還有其他實現CRISPR基因改造的辦法——其中一種被稱作“堿基編輯”(base editing)。在本周三的《自然》(Nature)和《科學》(Science)雜志上,哈佛-麻省理工大學Broad研究所(Broad Institute of MIT and Harvard)的研究人員對其進行了介紹。

如《麻省理工科技評論》(MIT Technology Review)所言,該系統幾乎可以被看作是CRISPR 2.0。科學家能夠把已有DNA的單個組成部分(人類基因組的堿基對是A-T和C-G,這四種分子結構單元構成了生命,決定了我們從外表到毀滅性疾病在內的一切特質)改成另一個。他們可以把“A”(代表腺嘌呤)改成某種類似“G”(鳥嘌呤)的物質。

這種化學上的取代會產生什么樣的結果呢?與被替代的“A”配對的“T”(胸腺嘧啶)也會變化,所以整個堿基對就變成了胞嘧啶-鳥嘌呤(C-G)。與CRISPR相比,這是個完全不同的里程碑。該技術更像是分子層面的剪刀,來切割和取代整個堿基對。這類堿基編輯工具可以針對非常精確的個體,或“點”,這些地方的突變是許多遺傳疾病發生的根本原因。(財富中文網)

譯者:嚴匡正

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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