纳米尺度DNA测序引爆医学革 命？ - 丁香园论坛-医学/药学...【medical-news】

Nanoscale DNA Sequencing: Health Revolution?

纳米尺度DNA测序引爆医学革 命？

Nanoscale DNA Sequencing Could Spur Revolution in Personal Health Care

纳米尺度的DNA测序可能加速个体化医疗革 命

译者：Docofsoul

ScienceDaily (Aug. 21, 2010) — In experiments with potentially broad health care implications, a research team led by a University of Washington physicist has devised a method that works at a very small scale to sequence DNA quickly and relatively inexpensively.

《每日科学》2010年8月21日报道 —— 由华盛顿大学的一名物理学家所率领的一个研究小组设计了一种方法，可在极小尺度上对DNA进行测序，并且测序速度更快、相对更加便宜。他们的实验表明，这一方法具有对卫生保健产生广泛影响的潜力。



This illustration depicts a single strand of DNA moving through a nanopore that is being used to sequence the DNA. (Credit: Image courtesy of University of Washington)

本示意图描述了单链DNA穿越用以测序的纳米孔（图片来源：华盛顿大学）

That could open the door for more effective individualized medicine, for example providing blueprints of genetic predispositions for specific conditions and diseases such as cancer, diabetes or addiction.

这一成果将为更有效的个体化医学，比如说为特定症状与疾病（如肿瘤、糖尿病或毒瘾）提供遗传倾向蓝图。

"The hope is that in 10 years people will have all their DNA sequenced, and this will lead to personalized, predictive medicine," said Jens Gundlach, a UW physics professor and lead author of a paper describing the new technique published the week of Aug. 16 in the Proceedings of the National Academy of Sciences.

华盛顿大学物理学教授Jens Gundlach以第一作者身份在8月16号的《美国国家科学院院刊》上发表了一篇论文来描述这项新的技术，他说： “希望在于：10年内大家可让自己的全部DNA都得到测序，并且个体化、预防性药品也将由此诞生。”

The technique creates a DNA reader that combines biology and nanotechnology using a nanopore taken from Mycobacterium smegmatis porin A. The nanopore has an opening 1 billionth of a meter in size, just large enough to measure a single strand of DNA as it passes through.

通过结合生物学与纳米技术并利用取之于耻垢分枝杆菌porin A（Mycobacterium smegmatis porin A.）的纳米孔，研究者以该论文所介绍的技术创建一个DNA电子阅读器。该阅读器上纳米孔有个十亿分之一米尺度的开口，刚好能让单链DNA通过以便测量。

The scientists placed the pore in a membrane surrounded by potassium-chloride solution. A small voltage was applied to create an ion current flowing through the nanopore, and the current's electrical signature changed depending on the nucleotides traveling through the nanopore. Each of the nucleotides that are the essence of DNA -- cytosine, guanine, adenine and thymine -- produced a distinctive signature.

研究小组的科学们将该小孔放置于浸润于氯化钾溶液的一块膜上，然后加上小电压以产生流过该纳米孔的离子流。该离子流的电签名（electrical signature）会根据穿越该纳米孔的核苷酸发生变化。 核苷酸是DNA的基本组成部分（DNA含四种脱氧核苷酸：胞核嘧啶、鸟嘌呤、腺嘌呤与胸腺嘧啶），每种核苷酸产生一个与众不同的签名。

The team had to solve two major problems. One was to create a short and narrow opening just large enough to allow a single strand of DNA to pass through the nanopore and for only a single DNA molecule to be in the opening at any time. Michael Niederweis at the University of Alabama at Birmingham modified the M. smegmatis bacterium to produce a suitable pore.

该研究小组必须解决两个主要难题：其一是建立短而狭窄的开口，刚好让DNA单链通过纳米孔，并且任何时间都只让单个DNA分子容身于该开口。阿拉巴马大学伯明翰分校的Michael Niederweis负责改造耻垢分枝杆菌以产生合适的小孔。

The second problem, Gundlach said, was that the nucleotides flowed through the nanopore at a rate of one every millionth of a second, far too fast to sort out the signal from each DNA molecule. To compensate, the researchers attached a section of double-stranded DNA between each nucleotide they wanted to measure. The second strand would briefly catch on the edge of the nanopore, halting the flow of DNA long enough for the single nucleotide to be held within the nanopore DNA reader. After a few milliseconds, the double-stranded section would separate and the DNA flow continued until another double strand was encountered, allowing the next nucleotide to be read.

Gundlach指出，第二个难题则是流过该纳米孔的核苷酸的速度必须是百万分之一秒内通过一个核苷酸，这样就太快了，无法检测来自每个DNA分子的信号。为了弥补这一点，研究者将位于想测量的每个核苷酸之间的双链DNA的一部分固定，第二条链会在短暂的时间内抓住纳米孔的边缘，使DNA流停留时间足够长，让单个核苷酸停在纳米孔DNA阅读器上。在几个毫秒后，双链部分会分开，于是DNA流继续流动直到下一个双链来到，这样下一个核苷酸的测量又开始了。

The delay, though measured in thousandths of a second, is long enough to read the electrical signals from the target nucleotides, Gundlach said.

Gundlach说该延迟虽然在测量时间上只有一秒的千分之几，却足够让阅读器读出来自目标核苷酸上的电信号。

"We can practically read the DNA sequence from an oscilloscope trace," he said.

他说：“我们实际上能够从示波器描迹上直接读出DNA序列。”

Besides Gundlach and Niederweiss, other authors are Ian Derrington, Tom Butler, Elizabeth Manrao and Marcus Collins of the UW; and Mikhail Pavlenok at Alabama-Birmingham.

除了Gundlach 与 Niederweiss，其他作者是华盛顿大学的Ian Derrington、Tom Butler、Elizabeth Manrao 、Marcus Collins 与阿拉巴马大学伯明翰分校的Mikhail Pavlenok。

The work was funded by the National Institutes of Health and its National Human Genome Research Institute as part of a program to create technology to sequence a human genome for $1,000 or less. That program began in 2004, when it cost on the order of $10 million to sequence a human-sized genome.

作为一项建立相关技术以求在1000美元之内的成本对人类基因组进行测序的计划的一倍分，本研究工作得到国立卫生研究院及其附属单位国立人类基因组研究研究院的资金支持。该计划始于2004年，当时耗资一千万美元对人类全基因组进行了测序。

The new research is a major step toward achieving DNA sequencing at a cost of $1,000 or less.

本项新的研究是向1000美元之内成本对DNA进行测序的目标迈出的重大一步。

"Our experiments outline a novel and fundamentally very simple sequencing technology that we hope can now be expanded into a mechanized process," Gundlach said.

Gundlach说：“我们的实验显示了一种新的、从根本上说非常简单的测序技术。我们希望，该技术现在能够拓展为一个机械化过程。”

（Docofsoul 译于2010-8-22）