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CRISPR如何让你编辑DNA – 译学馆
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CRISPR如何让你编辑DNA

How CRISPR lets you edit DNA - Andrea M. Henle

“这是最惊人的时刻 你们会盯着彼此说’天哪’”
From the smallest single-celled organism
从最小的单细胞生物
to the largest creatures on earth,
到地球上最庞大的生物
every living thing is defined by its genes.
每种生物都是由其基因所决定的
The DNA contained in our genes acts like an instruction manual for our cells.
基因中的DNA就像细胞的说明书
Four building blocks called bases are strung together in precise sequences,
四种基本元件-碱基精确连接在一起形成序列
which tell the cell how to behave and form the basis for our every trait.
来决定细胞如何活动 并构成形成生物基本特点的物质基础
But with recent advancements in gene editing tools,
但是近些年随着基因编辑工具的不断发展
scientists can change an organism’s fundamental features in record time.
科学家们已经可以改变机体的基础特征了
They can engineer drought-resistant crops
他们可以培育抗旱作物
and create apples that don’t brown.
种植出不会枯黄的苹果
They might even prevent the spread of infectious outbreaks
他们甚至可以预防传染病疫情的传播
and develop cures for genetic diseases.
研发遗传性疾病的治疗方法
CRISPR is the fastest, easiest,
在科技界这一轮新浪潮中
and cheapest of the gene editing tools
CRISPR 是目前效率最高 操作最简单
responsible for this new wave of science.
价格最低的基因编辑工具
But where did this medical marvel come from?
但是这个医学奇迹从何而来呢
How does it work?
它是如何运作的呢
And what can it do?
它可以做些什么呢
Surprisingly,CRISPR is actually a natural process
令人惊讶的是 CRISPR 其实是个自然发生的过程
that’s long functioned as a bacterial immune system.
它就像细菌的免疫系统一样长期发挥作用
Originally found defending single-celled bacteria and archaea
最初是在单细胞细菌和古生菌抵抗病毒中发现的
against invading viruses, naturally occurring CRISPR uses two main components.
自然发生的CRISPR包含两个主要组件
The first are short snippets of repetitive DNA sequences
首先是短的DNA重复序列
called “clustered regularly interspaced short palindromic repeats,”
规律成簇的间隔短回文重复序列
or simply, CRISPRs.
或简称CRISPRs
The second are Cas, or “CRISPR-associated” proteins
第二个是Cas 或者 CRISPR相关蛋白
which chop up DNA like molecular scissors.
它像分子剪刀一样剪开DNA链
When a virus invades a bacterium,
当病毒入侵细菌时
Cas proteins cut out a segment of the viral DNA
Cas 蛋白质会切断病毒DNA的一部分
to stitch into the bacterium’s CRISPR region,
使之连接到细菌的CRISPR区域
capturing a chemical snapshot of the infection.
同时捕捉到感染部分的化学特征
Those viral codes are then copied into short pieces of RNA.
这些病毒基因编码会被复制成RNA的短片段
This molecule plays many roles in our cells,
这个分子在我们的细胞中有许多作用
but in the case of CRISPR,
但是在CRISPR中
RNA binds to a special protein called Cas9.
RNA片段会和一种叫作Cas9的蛋白质结合
The resulting complexes act like scouts,
这样产生的复合体就像侦察兵
latching onto free-floating genetic material
由于是被附着在游离的遗传物质上
and searching for a match to the virus.
它可以寻找和病毒匹配的片段
If the virus invades again, the scout complex recognizes it immediately,
如果病毒再次入侵 侦察兵复合体会立即识别
and Cas9 swiftly destroys the viral DNA.
并且Cas9会迅速摧毁这个病毒的DNA
Lots of bacteria have this type of defense mechanism.
大多数的细菌都有这种防御机制
But in 2012, scientists figured out how to hijack CRISPR
但在2012年 科学家们发现了利用CRISPR
to target not just viral DNA,
攻击其它有机体的DNA的方法
but any DNA in almost any organism.
不仅仅局限病毒DNA
With the right tools,
运用正确的工具
this viral immune system becomes a precise gene-editing tool,
这种病毒防御系统变成一种精准的基因编辑工具
which can alter DNA and change specific genes
它可以更改DNA并修改特殊基因
almost as easily as fixing a typo.
就像修改排印错误一样简单
Here’s how it works in the lab:
接下来就说说在实验室中它是如何进行的:
scientists design a “ guide ” RNA to match the gene they want to edit,
科学家会设计向导RNA 来配对他们想要编辑的基因
and attach it to Cas9.
并把它接到Cas9上
Like the viral RNA in the CRISPR immune system,
就像CRISPR的免疫系统中的病毒RNA
the guide RNA directs Cas9 to the target gene,
向导RNA指挥Cas9到目标基因
and the protein’s molecular scissors snip the DNA.
然后蛋白质分子将DNA剪开
This is the key to CRISPR’s power:
CRISPR的能量来源是
just by injecting Cas9 bound to a short piece of custom guide RNA
通过注射Cas9 使之连接到特定向导RNA
scientists can edit practically any gene in the genome.
实际上科学家可以编辑基因组中的任何基因
Once the DNA is cut, the cell will try to repair it.
一旦DNA被剪断 细胞就会试图修复它
Typically,proteins called nucleases
尤其是 叫核酸酶的蛋白质
trim the broken ends and join them back together.
会修剪断裂的地方 并将它们连接起来
But this type of repair process, called nonhomologous end joining,
但是这个叫作非同源末端连接的修复过程
is prone to mistakes and can lead to extra or missing bases.
容易出错并导致碱基增加或者缺失
The resulting gene is often unusable and turned off.
这样的基因通常是不能用的 会被关闭
However,if scientists add a separate sequence of template DNA
然而 如果科学家在他们的CRISPR混合物中
to their CRISPR cocktail,
添加一个单独的DNA模板序列
cellular proteins can perform a different DNA repair process,
那么细胞蛋白就可以执行不同的DNA修复过程
called homology directed repair.
这叫做同源性定向修复
This template DNA is used as a blueprint to guide the rebuilding process,
用这个模板DNA 当作设计图来指导修复过程
repairing a defective gene or even inserting a completely new one.
修复一个缺陷基因甚至插入一个新的基因
The ability to fix DNA errors
能够做到这样修复DNA错误
means that CRISPR could potentially create new treatments for diseases
就意味着CRISPR有可能研发出针对特殊基因错误导致的疾病的新疗法
linked to specific genetic errors, like cystic fibrosis or sickle cell anemia.
例如囊胞性纤维症或者镰状细胞性贫血
And since it’s not limited to humans,
由于它并非局限于人类
the applications are almost endless.
其应用范围就几乎是无穷尽的
CRISPR could create plants that yield larger fruit,
CRISPR可以让植物结出更大的果实
mosquitoes that can’t transmit malaria,
可以让蚊子无法传播疟疾
or even reprogram drug-resistant cancer cells.
甚至可以对耐药癌细胞重新编程
It’s also a powerful tool for studying the genome,
对于研究基因组来说 它也是一个有力的工具
allowing scientists to watch what happens when genes are turned off
它能让科学家们看到生物体内
or changed within an organism.
发生基因关闭或者改变时的情况
CRISPR isn’t perfect yet.
CRISPR技术目前还不够完备
It doesn’t always make just the intended changes,
它并不总能得到预期的结果
and since it’s difficult to predict the long-term implications of a CRISPR edit,
因为很难预测到CRISPR编辑带来的长期影响
this technology raises big ethical questions.
这项技术引发了重大的伦理问题
It’s up to us to decide the best course forward
这就需要我们去决断它最好的愿景
as CRISPR leaves single-celled organisms behind
因为这个技术会不仅仅存在于单细胞生物中
and heads into labs, farms, hospitals,
它会应用于实验室 农场 医院
and organisms around the world.
它会应用于全世界的生物体

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