基因編輯展示更大治療潛力

Crispr, the gene-editing tool transforming biotechnology, is showing even greater promise for treating genetic disease thanks to two developments unveiled yesterday.

昨日公布的兩項(xiàng)研究進(jìn)展意味著，給生物技術(shù)領(lǐng)域帶來(lái)巨變的基因編輯工具Crispr在治療遺傳性疾病方面展示出了更大的潛力。

The advances were published by two teams of scientists from Massachusetts Institute of Technology and Harvard University, working together at the Broad Institute, their joint facility.

這些進(jìn)展是由來(lái)自麻省理工學(xué)院(MIT)和哈佛大學(xué)(Harvard University)的兩個(gè)科學(xué)家團(tuán)隊(duì)發(fā)表的，他們?cè)陔p方的聯(lián)合設(shè)施布羅德研究所(Broad Institute)一起工作。

One of the groups has adapted Crispr to make it easier to change individual chemical “letters” of DNA in genetic code, rather than inserting or deleting whole genes. Their tool, described in the journal Nature, is known as base editing and can be likened to using a sharp pencil rather than scissors on the genome.

其中一個(gè)小組改良了Crispr，以便更容易改變遺傳代碼中DNA的個(gè)別化學(xué)“字母”，而不是插入或刪除整個(gè)基因。根據(jù)《自然》(Nature)期刊上所載論文，他們的工具被稱(chēng)為“堿基編輯”(base editing)，可以比作為對(duì)基因組使用“削尖的鉛筆”，而不是“剪刀”。

The other team, publishing in Science, has made it possible to edit not only DNA, the chemical that stores the genome in all living creatures, but RNA, which converts genetic information into proteins — the workhorse molecules of biology. This is described as like correcting a book with temporary ink that disappears, rather than making an indelible mark.

在《科學(xué)》(Science)期刊上發(fā)表論文的另一個(gè)團(tuán)隊(duì)取得的進(jìn)展是，不僅可以編輯DNA(脫氧核糖核酸，將基因組存儲(chǔ)在所有生物中的化學(xué)物質(zhì))，而且可以編輯RNA(核糖核酸，將遺傳信息轉(zhuǎn)化為蛋白質(zhì)——埋頭苦干的生物學(xué)分子)。這被形容為用一種會(huì)褪色的臨時(shí)墨水來(lái)更改一本書(shū)，而不是留下擦不掉的痕跡。

“This is an exciting week for genetic research,” said Helen O’Neill, director of reproductive science and women’s health at University College London, yesterday. “These papers highlight the fast pace of the field and the continuous improvements being made in genome editing, bringing it closer and closer to the clinic.”

“對(duì)遺傳學(xué)研究來(lái)說(shuō)，這是令人振奮的一周，”倫敦大學(xué)學(xué)院(University College London)生殖科學(xué)和婦女保健主任海倫•奧尼爾(Helen O'Neill)昨日表示。“這些論文突顯了該領(lǐng)域的快速發(fā)展和基因組編輯方面的不斷改進(jìn)，使其越來(lái)越接近臨床應(yīng)用。”

“I hope these complementary technologies will together enable a broad suite of research and therapeutic applications,” said David Liu, professor of chemical biology at Harvard, who led the DNA base-editing team.

“我希望這些互補(bǔ)的技術(shù)能夠結(jié)合起來(lái)，帶來(lái)一整套研究和治療應(yīng)用，”帶領(lǐng)DNA堿基編輯團(tuán)隊(duì)的哈佛大學(xué)化學(xué)生物學(xué)教授David Liu表示。

“For some situations where transient editing is desirable, such as acute inflammation, RNA editing may be ideal,” Prof Liu said. “For other applications, such as genetic disease, you’d want to make a one-time change in the genome through DNA base editing.”

“對(duì)于需要臨時(shí)編輯的某些情況，如急性炎癥，RNA編輯可能是最理想的，”David Liu表示。“對(duì)于其他應(yīng)用，如遺傳疾病，您就需要通過(guò)DNA堿基編輯，對(duì)基因組作出一次性改變。”

Base editing changes the genome by a single DNA “base” or letter in the four-letter genetic code. Last year Prof Liu’s team published a simple method for converting the letter C to T, and scientists are working to apply the technique in the laboratory.

堿基編輯通過(guò)改動(dòng)單個(gè)DNA“堿基”(四字母遺傳密碼中的字母)來(lái)改變基因組。去年David Liu的團(tuán)隊(duì)發(fā)表了一種將字母C轉(zhuǎn)換為T(mén)的簡(jiǎn)單方法，科學(xué)家們正致力于將這種方法應(yīng)用于實(shí)驗(yàn)室。

Last month a Chinese team used it to correct a form of the blood disorder thalassaemia in human embryos.

上月，一個(gè)中國(guó)團(tuán)隊(duì)利用這種方法糾正人胚胎中的地中海貧血(一種血液疾病)。

Now the scientists have discovered how to change A to G, which will greatly extend the range of genetic disorders that could potentially be treated by base editing. These single-letter or point mutations are responsible for thousands of diseases.

現(xiàn)在科學(xué)家們發(fā)現(xiàn)了如何將A改為G，這將大大延伸有望通過(guò)堿基編輯治療的遺傳疾病的范圍。這類(lèi)單字母(點(diǎn))突變導(dǎo)致數(shù)千種疾病。

The Broad Institute team is particularly interested in applying the technology to genetic deafness and blindness and inherited blood diseases.

布羅德研究所團(tuán)隊(duì)特別感興趣的是將該技術(shù)應(yīng)用于遺傳性耳聾、失明和遺傳性血液病。

The advance in RNA editing comes from a team led by Feng Zhang, who played a key role in the development of Crispr technology. It converts the letter A to G in RNA, the biochemical intermediary between genes and proteins.

RNA編輯的進(jìn)展來(lái)自張鋒(Feng Zhang)帶領(lǐng)的團(tuán)隊(duì);他曾在Crispr技術(shù)的發(fā)展中扮演關(guān)鍵角色。新的方法能夠?qū)NA(基因和蛋白質(zhì)之間的生物化學(xué)中介體)中的字母A轉(zhuǎn)換為G。

The researchers say RNA editing offers a safer and more flexible way to make corrections than the permanent changes involved in DNA editing. “It can fix mutations without tampering with the genome, and because RNA naturally degrades, it is a potentially reversible fix,” said David Cox, part of the Broad Institute team.

研究者們表示，就作出修正而言，RNA編輯提供了比DNA編輯所涉及的永久變化更安全、更靈活的方法。“它可以修復(fù)突變而不會(huì)干擾基因組，而且因?yàn)镽NA可自然降解，這是一種潛在可逆的修復(fù)，”布羅德研究所團(tuán)隊(duì)成員戴維•考克斯(David Cox)表示。

While experiments with RNA and DNA base editing are under way in animals and human cell cultures, the scientists say clinical trials on patients are not expected to begin in the near future.

雖然目前已在動(dòng)物和人類(lèi)細(xì)胞培養(yǎng)物中進(jìn)行RNA和DNA堿基編輯實(shí)驗(yàn)，但科學(xué)家們預(yù)計(jì)，不會(huì)在不久的將來(lái)進(jìn)行患者臨床試驗(yàn)。