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来源RNA offers a safer way to reprogram cells
译者马尔代夫
RNA offers a safer way to reprogram cells
However, the techniques now used to transform cells pose some serious safety hazards. To deliver the genes necessary to reprogram cells to a pluripotent state, scientists use viruses carrying DNA, which then becomes integrated into the cell’s own DNA. But this so-called DNA-based reprogramming carries the risk of disrupting the cell’s genome and leading it to become cancerous.
但是,现在这种细胞转化技术仍存在安全隐患。为了导入必须基因来重新编码细胞使之达到多能状态,科学家使用了携带DNA的病毒,这些DNA随后会合成为细胞自身的DNA.但是这种所谓的以DNA为基准的重新编码冒着打乱细胞染色体和使细胞癌化的风险。
Now, for the first time, MIT researchers have shown that they can deliver those same reprogramming genes using RNA, the genetic material that normally ferries instructions from DNA to the cell’s protein-making machinery. This method could prove much safer than DNA-based reprogramming, say the researchers, Associate Professor of Electrical and Biological Engineering Mehmet Fatih Yanik and electrical engineering graduate student Matthew Angel
现在,麻省理工的研究员第一次表示他们能够用RNA来完成相同的基因重新编码,RNA在正常情况下接收DNA的指令来合成细胞蛋白质。电子和生物工程的副教授Yanik和电子工程的本科生Angel指出,这种方法比用DNA为基准的方法更安全。
Yanik and Angel describe the method, also the subject of Angel’s master’s thesis, in the July 23 issue of the journal PLoS ONE.
Yanik和Angle描述的这种的方法也是Angel的硕士论文题目,发表在<PLOS ONE>7月23号那期上。
However, the researchers say they cannot yet claim to have reprogrammed the cells into a pluripotent state. To prove that, they would need to grow the cells in the lab for a longer period of time and study their ability to develop into other cell types — a process now underway in their lab. Their key achievement is demonstrating that the genes necessary for reprogramming can be delivered with RNA.
“Before this, nobody had a way to transfect cells multiple times with protein-encoding RNA,” says Yanik. (Transfection is the process of introducing DNA or RNA into a cell without using viruses to deliver them.)
Focus on RNA
关注RNA
In 2006, researchers at Kyoto University showed they could reprogram mouse skin cells into a pluripotent, embryonic-like state with just four genes. More recently, other scientists have achieved the same result in human cells by delivering the proteins encoded by those genes directly into mature cells, but that process is more expensive, inefficient and time-consuming than reprogramming with DNA.
2006年,京都大学的研究人员表示他们仅靠4中基因就能重新编码老鼠的皮肤细胞使之还原到胚胎多能状态。之后,其他科学家在人类细胞的实验中也得到了相同的结果。他们用这4种基因直接将编码蛋白质导入到成熟细胞中,但是这一方法没有DNA重新编码有效,且费用更高,更耗时。
Funded by a Packard Fellowship in Science and Engineering, Yanik and Angel decided to pursue a new alternative by transfecting cells with messenger RNA (mRNA), a short-lived molecule that carries genetic instructions copied from DNA.
However, they found that RNA transfection poses a significant challenge: When added to mature human skin cells, mRNA provokes an immune response meant to defend against viruses made of RNA. Repeated exposure to long strands of RNA leads cells to undergo cell suicide, sacrificing themselves to help prevent the rest of the body from being infected.
Yanik and Angel knew that some RNA viruses, including hepatitis C, can successfully suppress that defensive response. After reviewing studies of hepatitis C’s evasive mechanisms, they did experiments showing they could shut off the response by delivering short interfering RNA (siRNA) that blocks production of several proteins key to the response.
Once the defense mechanism is shut off, mRNA carrying the genes for cell reprogramming can be safely delivered. The researchers showed that they could induce cells to produce the reprogramming proteins for more than a week, by delivering siRNA and mRNA every other day.
只要关闭了这种自卫机制,能够重新编码细胞且携带遗传基因的信使RNA就能安全导入了。研究人员们表示他们每隔一天导入小核RNA和信使RNA,就能够诱导细胞持续一周产生重新编码蛋白质。
Peter Andrews, director of the Centre for Stem Cell Biology at the University of Sheffield, says the MIT team’s key advance is suppressing the cell’s immune response to RNA. He calls the work an interesting approach, but adds “the jury’s out” on whether it will prove better than other methods. “The next step would be to make iPS cells [induced pluripotent stem cells]” using this technique, says Andrews. The MIT researchers agree that determining whether this will work remains an open question.
谢菲尔德大学干细胞生物中心的主任Peter Andrews说,麻省理工研究小组的主要进展就是克服了细胞对RNA的免疫反应。他称这个方法很有趣,但是又补充道,不排除还有更好的方法。他还说,下一步就将用这种方法来诱导多能性干细胞。麻省理工的研究人员有同样的预期,但能否成功仍不得而知。
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Never in a month of Sundays would I have imagined landing here from a search on yahoo for “government health and safety.” Enjoyed the article though, thanks, will come back another time to read more. Busy now.