How CRISPR lets you edit DNA - Andrea M. Henle

譯者: Lilian Chiu 審譯者: Regina Chu

From the smallest single-celled organism

從最小的單細胞有機體，

to the largest creatures on earth,

到地球上最大的動物，

every living thing is defined by its genes.

所有生物都是 由它的基因所定義的。

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

我們基因中的 DNA 就像是 給我們細胞看的說明書。

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

四種叫做「鹼基」的積木， 會依照特定的順序串在一起，

which tell the cell how to behave

告訴細胞該做出什麼行為，

and form the basis for our every trait.

並形成我們每一項特點的基礎。

But with recent advancements in gene editing tools,

但靠著近期在基因工具的進展，

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

科學家能夠在最短時間內 改變有機體的基本特徵。

They can engineer drought-resistant crops

他們能設計出抗旱的作物，

and create apples that don’t brown.

創造出不會變成褐色的蘋果。

They might even prevent the spread of infectious outbreaks

他們甚至可能可以預防 感染性疾病爆發的擴散，

and develop cures for genetic diseases.

並開發出基因疾病的解藥。

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

CRISPR 是最快速、最簡單， 且最便宜的基因編輯工具，

responsible for this new wave of science.

會有這一波科學新潮流， 就是因為它。

But where did this medical marvel come from?

但這項醫學奇蹟是從哪裡來的？

How does it work?

它如何運作？它能做什麼？

And what can it do?

Surprisingly, CRISPR is actually a natural process

很讓人訝異的是，CRISPR 其實是一種自然過程，

that’s long functioned as a bacterial immune system.

長久以來就以細菌 免疫系統的形式在運作。

Originally found defending single-celled bacteria and archaea

最早發現它會保護 單細胞細菌和古菌，

against invading viruses,

抵抗來襲的病毒，

naturally occurring CRISPR uses two main components.

自然發生的 CRISPR 會使用兩種主要元件。

The first are short snippets of repetitive DNA sequences

第一種是重覆 DNA 序列的片斷，

called “clustered regularly interspaced short palindromic repeats,”

叫做「群聚且有規律間隔的 短回文重覆序列」，

or simply, CRISPRs.

或簡稱為 CRISPRs。

The second are Cas,

第二種是 Cas，

or “CRISPR-associated” proteins

即 CRISPR 關聯蛋白，

which chop up DNA like molecular scissors.

它像是分子剪刀一樣 可以切碎 DNA。

When a virus invades a bacterium,

當病毒攻擊細菌時，

Cas proteins cut out a segment of the viral DNA

Cas 蛋白會把病毒 DNA 的一部分切下來，

to stitch into the bacterium’s CRISPR region,

將它縫到細菌的 CRISPR 區域，

capturing a chemical snapshot of the infection.

取得感染的化學快照。

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

接著，那些病毒碼 會被複製成短的 RNA。

This molecule plays many roles in our cells,

RNA 這種分子在我們的 細胞中扮演許多角色，

but in the case of CRISPR,

但就 CRISPR 的情況來說，

RNA binds to a special protein called Cas9.

RNA 會和特別的蛋白質 Cas9 結合 。

The resulting complexes act like scouts,

產生出來的複合物， 功能就像是偵察兵，

latching onto free-floating genetic material

佔據自由浮動的基因材料，

and searching for a match to the virus.

搜尋和病毒一模一樣的目標。

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

如果病毒再次侵襲， 偵察兵複合物就會馬上認出它，

and Cas9 swiftly destroys the viral DNA.

Cas9 會快速地摧毀病毒 DNA。

Lots of bacteria have this type of defense mechanism.

很多細菌都有這種防禦機制。

But in 2012, scientists figured out how to hijack CRISPR

但，2012 年，科學家 找出了方法來劫持 CRISPR，

to target not just viral DNA,

讓它的目標不只是病毒 DNA，

but any DNA in almost any organism.

而是幾乎任何 有機體中的任何 DNA。

With the right tools,

用對了工具，這種病毒免疫系統

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

就變成了精確的基因編輯工具，

which can alter DNA and change specific genes

能用來修改 DNA， 改變特定的基因，

almost as easily as fixing a typo.

幾乎就像打錯字的修改一樣容易。

Here’s how it works in the lab:

在實驗室中，它是這樣運作的：

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

科學家設計出一個「嚮導」RNA， 符合他們想要編輯的基因，

and attach it to Cas9.

將它附著到 Cas9 上。

Like the viral RNA in the CRISPR immune system,

就像 CRISPR 免疫系統中的病毒 RNA，

the guide RNA directs Cas9 to the target gene,

嚮導 RNA 會指示 Cas9 去找目標基因，

and the protein’s molecular scissors snip the DNA.

該蛋白質的分子剪刀會切斷 DNA。

This is the key to CRISPR’s power:

這就是 CRISPR 如此強大的關鍵：

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

只要把 Cas9 注射到短短一小段 訂製的嚮導 RNA 中，

scientists can edit practically any gene in the genome.

科學家就可以編輯 基因組中的幾乎任何基因。

Once the DNA is cut,

一旦 DNA 被切斷， 細胞會嘗試修復它。

the cell will try to repair it.

Typically, proteins called nucleases

通常，叫做核酸酶的蛋白質

trim the broken ends and join them back together.

會把破裂的邊緣修整好， 將它們重新接合起來。

But this type of repair process,

但這種修復過程，

called nonhomologous end joining,

也就是「非同源染色體末端連接」，

is prone to mistakes

很容易犯錯，且可能會導致 鹼基多出來或不足。

and can lead to extra or missing bases.

The resulting gene is often unusable and turned off.

結果產生出來的基因通常不能用， 會被關掉（去活化）。

However, if scientists add a separate sequence of template DNA

然而，如果科學家將一個 個別的模板 DNA 序列

to their CRISPR cocktail,

加到他們的 CRISPR 雞尾酒裡，

cellular proteins can perform a different DNA repair process,

細胞蛋白質就能執行 一種不同的 DNA 修復過程，

called homology directed repair.

稱為同源介導修復。

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

這種模板 DNA 被用來當作藍圖， 引導重建的過程。

repairing a defective gene

修復缺陷基因，

or even inserting a completely new one.

或甚至插入全新的基因。

The ability to fix DNA errors

有修復 DNA 錯誤的能力，

means that CRISPR could potentially create new treatments for diseases

就表示可能可以用 CRISPR 來創造新的療法，

治療與特定基因錯誤有關的疾病，

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

比如囊腫性纖維化 或鐮狀細胞性貧血症。

And since it’s not limited to humans,

既然它不只限於人類，

the applications are almost endless.

應用範圍幾乎是無限大的。

CRISPR could create plants that yield larger fruit,

CRISPR 可以創造出 果實更大的植物，

mosquitoes that can’t transmit malaria,

不會傳播瘧疾的蚊子，

or even reprogram drug-resistant cancer cells.

或甚至將有抗藥性的 癌細胞重新編程。

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

在研究基因組方面， 它也是強大的工具，

allowing scientists to watch what happens when genes are turned off

讓科學家可以看到， 當基因被關掉時，

or changed within an organism.

或在有機體內改變時， 會發生什麼事。

CRISPR isn’t perfect yet.

CRISPR 還不完美。

It doesn’t always make just the intended changes,

它不見得能只做出 我們想要做的改變，

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

且因為很難預測長期來看 CRISPR 編輯會有什麼意涵，

this technology raises big ethical questions.

這項技術免不了會有 很大的倫理問題。

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

我們要決定未來 怎麼走才是最好的，

as CRISPR leaves single-celled organisms behind

因為 CRISPR 不再 只用於單細胞有機體，

and heads into labs, farms, hospitals,

它已經要邁入全世界的 實驗室、農田、

醫院，以及生物。

and organisms around the world.