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发表于 2002-8-10 11:41
From : Scientific American
http://www.sciam.com/article.cfm?articleID=0006F940-DDC2-1D29-97CA809EC588EEDF#authorinfo
NEWS SCAN
August 2002 issue
Killing the Messenger
Turning off RNA could thwart cancer and AIDS
By Carol Ezzell
Like a jealous chef, the nucleus guards the recipes for making all the proteins a cell needs. It holds
tightly to the original recipe book, written in DNA, doling out copies of the instructions in the
form of messenger RNA (mRNA) to the cell's cytoplasm only as they are needed.
就象一个嫉妒的厨师那样，细胞核守护着用来制造细胞所需的所有蛋白质的秘方。它紧紧地
护着原始的秘方书册，用脱氧核糖核酸写就。在需要的时候，会少量地以信使RNA（mRNA）
的形式发布指令副本给细胞质。
But in cancer cells and in cells infected by viruses, those carefully
issued orders are often drowned out. Mutations can cause cancer cells to
issue garbled directions that result in aberrant proteins. Similarly,
viruses flood cells with their own mRNA, hijacking the cells'
protein-making apparatuses to make copies of new viruses that can go on
to infect other cells.
但在癌细胞和感染病毒的细胞中，这些谨慎发布的指令往往被湮没了。（基因）
突变能造成癌细胞发布混乱的指令，导致异常的蛋白质。类似的，病毒将它们自
己的信使RNA（mRNA）注入细胞，夺取了细胞蛋白质制造的机构，用来制造病毒
的新副本，以便感染其他细胞。
Researchers are currently attempting to harness a recently discovered
natural phenomenon called RNA interference (RNAi) to intercept, or "knock
down," such bad messages. They are using the technique to identify the
functions of genes in fruit flies and microscopic worms--a strategy that
will help them uncover what the corresponding genes do in humans. And
medical scientists are hoping to deploy RNAi as a treatment for AIDS and
cancer or as a preventive against the rejection of transplants.
研究人员正努力去驾驭一个最新的发现自然现象称为RNA干涉(RNAi)，来截断，
或“拆卸”这些坏的信使。他们正在用技术手段来鉴别果蝇和微蠕虫基因的功能，
——这个策略有助于他们揭露人类相应基因的功能。医学家希望将RNAi作为
AIDS、癌症的疗法，或是器官移植排异的预防手段。
RNAi was first identified in 1998 in nematodes, in which it appears to
serve as a way to block the proliferation of so-called jumping genes
(transposons). In other organisms, cellular enzymes that are part of the
RNAi machinery specifically target stray bits of double-stranded RNA,
which could arise from viruses, and pull the strands apart. Then, in a
process that scientists are just now beginning to understand, the freed
strands go on to bind to and inactivate any mRNA that has the complementary
genetic sequence.
RNAi最早于1998年在线虫中发现。在线虫身上，RNAi作用是阻塞所谓的“跳跃
基因”（转位子transposons）。在其他生物体中，细胞酶是RNAi机制一部分，
特定的瞄准，扰乱部分（来自病毒的）双螺旋RNA，使双螺旋分裂。然后，在科
学家刚刚认识的一种步骤中，解开的螺旋继续绑定和阻碍任何含有附加基因序列
的mRNA（信使RNA）
Several groups of researchers have reported within the past few months
that the same phenomenon could have therapeutic benefits in mammalian
cells by shutting down viral genes or those linked to tumor formation.
Two groups--one led by John J. Rossi of the Beckman Research Institute
at the City of Hope Cancer Center in Duarte, Calif., and another by Phillip
A. Sharp of the Massachusetts Institute of Technology--engineered human
B. cells to make double-stranded RNAs that match sequences from HIV. They
C. found that those RNAs completely prevented the cells from making HIV
D. proteins after the cells were infected. Other scientists have used RNAi
E. to knock down cancer-related proteins such as beta-catenin and p53.
过去的几个月里，多组科研人员报道了同样的现象在哺乳动物细胞中有疗效，通
过关掉病毒基因或肿瘤形成相关基因。两组人员——由Beckman Research
Institute的John J. Rossi领导的（at the City of Hope Cancer Center in
Duarte, Calif.），和由麻省理工的Phillip A. Sharp领导的——操作人体细
胞制造双螺旋RNAs，与HIV的次序相匹配。他们发现这些RNAs全面防止了被感
染细胞制造HIV蛋白质。其他科学家使用RNAi来对抗癌症相关的蛋白，如
β- catenin和p53.
Rossi says that his group plans to try the approach in people with HIV
in the next couple years. One strategy he and his colleagues are
considering is to remove T cells (which are normally decimated by HIV)
from the individuals, use viruses to ferry into them genetic sequences
for double-stranded RNAs that encode HIV proteins, and then infuse the
altered cells back into the patients' bodies. "We'd like to create a pool
of T cells that would resist HIV," thereby enabling HIV-infected people
to stay healthy, he says.
Rossi说，他的小组计划在下面两年中尝试人类的HIV病毒。他及同事的一个策
略是，从人体中转移出T细胞（通常被HIV大量破坏），用某种病毒载运进基因
序列，其序列生成编码与HIV蛋白编码匹配的RNAs双螺旋。然后将基因转变后
的细胞回输给患者体内。他说，“我们希望制造一群T细胞来抵抗HIV，由此使
HIV感染者维持健康。
In another application, two of Rossi's colleagues, Laurence Cooper and
Michael Jensen, are using RNAi to generate a kind of cellular universal
soldier for attacking cancer. Cooper, Jensen and their co-workers are
invoking the technique to prevent killer T cells from making proteins that
mark them as "self" or "nonself." These universal killer cells, they hope,
will be infused into cancer patients without being eliminated as foreign.
其他项目中，Rossi的两位同事，Laurence Cooper 和 Michael Jensen,正利用
RNAi生成细胞通用的战士来对付癌症。他们用技术手段来阻止杀手T细胞制造
蛋白标记“自己人”或“非自己人”。他们希望这种杀手细胞能被注入患者而不
受排斥。
Brenda L. Bass, a Howard Hughes Medical Institute investigator at the
University of Utah, comments that RNAi has been shown so far in laboratory
experiments to be more efficient at stifling gene expression than another
technique called antisense RNA. Several antisense drugs, which also
function by binding to mRNA, are now in human tests, but their mechanism
of action is still poorly understood, and they are somewhat fickle. "With
antisense, you don't know if it will work on your given gene," Bass says.
"It is clear that RNAi is much, much more effective."
Brenda L. Bass（Howard Hughes Medical Institute investigator at the University of Utah），认为
RNAi在实验室中表现出了更高的效能（比起另外的称作antisense RNA的药物）。很多
antisense RNA药物（它们也是绑定mRNA），正在作人体实验，但它们的行为机制仍不明确，
它们的表现变幻无常。Bass 说，“利用antisense 时，你不能确定她是否能作用于特定的基
因。很明显，RNAi更加有效。”
The Author(s):
Carol Ezzell is a staff editor and writer.
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