How CRISPR lets you edit DNA - Andrea M. Henle

翻译人员: Riley WANG 校对人员: Lipeng Chen

From the smallest single-celled organism

从最小的单细胞有机体，

to the largest creatures on earth,

到地球上最大的生物，

every living thing is defined by its genes.

每一个生命都由其基因决定。

The DNA contained in our genes acts like an instruction manual for our cells.

基因中包含的DNA遗传物质 就像是细胞的使用说明。

Four building blocks called bases are strung together in precise sequences,

4种碱基以精确的顺序连结成串，

which tell the cell how to behave

指挥细胞的行为，

and form the basis for our every trait.

构成我们每项特质的基础。

But with recent advancements in gene editing tools,

但通过运用最先进的 基因编辑工具，

scientists can change an organism’s fundamental features in record time.

科学家可以用最短的时间 改变有机体的根本特征。

They can engineer drought-resistant crops

他们可以开发出抗旱的农作物，

and create apples that don’t brown.

创造出不会氧化变色的苹果。

They might even prevent the spread of infectious outbreaks

他们甚至能够 防止传染病大规模扩散，

and develop cures for genetic diseases.

并研发出遗传性疾病的治疗方法。

CRISPR is the fastest, easiest, and cheapest of the gene editing tools

CRISPR是最快、最简单、 最便宜的基因编辑工具，

responsible for this new wave of science.

引领了新一波科学研究潮流。

But where did this medical marvel come from?

这个医学奇迹从何而来？

How does it work?

它是如何工作的？

And what can it do?

它能做些什么？

Surprisingly, CRISPR is actually a natural process

令人惊奇的是，CRISPR实际上是一种自然现象，

that’s long functioned as a bacterial immune system.

长久以来其功能是 作为细菌的免疫系统。

Originally found defending single-celled bacteria and archaea

人们最早发现 单细胞细菌和古生菌

against invading viruses,

利用CRISPR抵抗入侵病毒。

naturally occurring CRISPR uses two main components.

自然界中的CRISPR 有两个主要组成部分：

The first are short snippets of repetitive DNA sequences

一个是基因序列的重复片段，

called “clustered regularly interspaced short palindromic repeats,”

称为 “常间回文重复序列丛集”，

or simply, CRISPRs.

简写为CRISPRs。

The second are Cas,

第二个是Cas蛋白，

or “CRISPR-associated” proteins

也称"常间回文重复序列丛集关联蛋白"。

which chop up DNA like molecular scissors.

它像一把分子剪刀将DNA切断。

When a virus invades a bacterium,

当病毒侵入细菌，

Cas proteins cut out a segment of the viral DNA

Cas蛋白剪下 一段病毒DNA片段,

to stitch into the bacterium’s CRISPR region,

将其缝合到细菌的CRISPR区域，

capturing a chemical snapshot of the infection.

捕捉到侵染的化学快照。

Those viral codes are then copied into short pieces of RNA.

这些病毒编码 会被复制到一小段RNA上。

This molecule plays many roles in our cells,

这个分子在我们细胞中有众多功能，

but in the case of CRISPR,

但对于CRISPR来说，

RNA binds to a special protein called Cas9.

RNA与一种特殊蛋白质Cas9结合。

The resulting complexes act like scouts,

形成的复合物仿佛是一群侦查员，

latching onto free-floating genetic material

它们与遗传物质结合，

and searching for a match to the virus.

寻找与病毒配对。

If the virus invades again, the scout complex recognizes it immediately,

如果病毒再次入侵， 这些侦查物质会立刻将其识别，

and Cas9 swiftly destroys the viral DNA.

Cas9可以迅速摧毁病毒的DNA。

Lots of bacteria have this type of defense mechanism.

许多细菌都有这种防御机制。

But in 2012, scientists figured out how to hijack CRISPR

但在2012年，科学家找出了

如何让CRISPR 不仅仅针对病毒DNA，

to target not just viral DNA,

but any DNA in almost any organism.

而是用于 几乎所有组织中的DNA。

With the right tools,

通过运用适当的工具，

this viral immune system becomes a precise gene-editing tool,

病毒免疫系统成为了 一个精细的基因编辑工具。

which can alter DNA and change specific genes

它能够改变DNA和特定基因，

almost as easily as fixing a typo.

这一过程简单地如同修改错别字。

Here’s how it works in the lab:

在实验室中，其运用方法如下：

scientists design a “guide” RNA to match the gene they want to edit,

科学家设计出一个向导RNA 来匹配他们想要编辑的基因，

and attach it to Cas9.

并将其附着在Cas9上。

Like the viral RNA in the CRISPR immune system,

它如同CRISPR 免疫系统中的病毒RNA一样，

the guide RNA directs Cas9 to the target gene,

向导RNA会引导Cas9到目标DNA，

and the protein’s molecular scissors snip the DNA.

蛋白质的分子剪刀将DNA切断。

This is the key to CRISPR’s power:

这是CRISPR强大的关键，

just by injecting Cas9 bound to a short piece of custom guide RNA

仅通过注入Cas9 与一小段定制的RNA绑定，

scientists can edit practically any gene in the genome.

科学家就能够改变几乎任何基因。

Once the DNA is cut,

DNA一旦被切断，

the cell will try to repair it.

细胞会试图进行修复。

Typically, proteins called nucleases

通常，一种叫做核酸酶的蛋白质

trim the broken ends and join them back together.

会修整断掉的两段 并将其重新连接。

But this type of repair process,

这种类型的修补过程

called nonhomologous end joining,

也称做非同源性末端接合

is prone to mistakes

很容易产生错误，

and can lead to extra or missing bases.

并导致多余或丢失碱基。

The resulting gene is often unusable and turned off.

产生的基因通常无法使用或表达。

However, if scientists add a separate sequence of template DNA

但是如果科学家 将一条模板DNA序列

to their CRISPR cocktail,

增加到CRISPR组合中，

cellular proteins can perform a different DNA repair process,

分子蛋白就能够 执行一个不同的DNA修复过程，

called homology directed repair.

称为同源介质的双链DNA修复。

This template DNA is used as a blueprint to guide the rebuilding process,

这个模板DNA能够引导重建过程，

repairing a defective gene

修复有缺陷的基因，

or even inserting a completely new one.

甚至插入一个全新的基因。

The ability to fix DNA errors

这种修复基因错误的能力

means that CRISPR could potentially create new treatments for diseases

意味着CRISPR 能够用于创造新的疗法，

linked to specific genetic errors, like cystic fibrosis or sickle cell anemia.

用于特定基因错误导致的疾病 如囊肿性纤维化或镰刀型红细胞贫血症。

And since it’s not limited to humans,

这项应用不只局限与人类，

the applications are almost endless.

它有几乎无限的可能。

CRISPR could create plants that yield larger fruit,

CRISPR能够创造 长出更大水果的植物，

mosquitoes that can’t transmit malaria,

无法传播疟疾的蚊子，

or even reprogram drug-resistant cancer cells.

甚至是重新编辑拥有抗药性的癌细胞。

It’s also a powerful tool for studying the genome,

它也是一个研究基因组的有力工具，

allowing scientists to watch what happens when genes are turned off

使得科学家能够观察在有机体中

or changed within an organism.

停止或改变基因表达会发生什么。

CRISPR isn’t perfect yet.

CRISPR尚不完美，

It doesn’t always make just the intended changes,

它无法总是做出人们想要的改变，

and since it’s difficult to predict the long-term implications of a CRISPR edit,

由于难以预测 CRISPR编辑的长期影响，

this technology raises big ethical questions.

这项技术引起了巨大的道德争议。

It’s up to us to decide the best course forward

随着CRISPR脱离单细胞生物，

as CRISPR leaves single-celled organisms behind

进入实验室、农场、医院，

and heads into labs, farms, hospitals,

以及世界上的各类有机体，

决定前进的最好道路 取决于我们自己。

and organisms around the world.