《Nature》新一代RNAi技术

【字体: 时间:2009年02月11日 来源:生物通

编辑推荐:

  生物通报道,来自罗格斯大学,新泽西大学等处的研究者在《Nature》旗下的子刊Nature Biotechnology发布了一篇文章,介绍了一种新型的RNAi技术,该技术具有广阔的应用前景,可明显的提高基因沉默的效率。这个技术最核心的关键是针对靶器官的RNA合成技术。

  

生物通报道,来自罗格斯大学,新泽西大学等处的研究者在《Nature》旗下的子刊Nature Biotechnology发布了一篇文章,介绍了一种新型的RNAi技术,该技术具有广阔的应用前景,可明显的提高基因沉默的效率。这个技术最核心的关键是针对靶器官的RNA合成技术。

 

新泽西大学一名分子生物与生化学系的副教授Gunderson创建了一种高效的基因沉默技术,他发现一种新的基因沉默因子,这一新的因子通过一种新型的机制来达到提高基因沉默的效果。这一因子被称为U1 AdaptorU1 接头,生物通译),U1接头具有双重独立的功能结构区域。它的第一个功能结构区域是靶基因的结合位点,该位点能针对任一基因量身定制。它的第二个功能结构区域是一个携带snRNP的域通过snRNP抑制mRNA成熟,以达在表达水平沉默基因的能力。

 

U1接头的优点

它可pre-mRNApolyA尾巴形成阶段阶段抑制mRNA的成熟过程。并且,带有snRNP的结构域是独立的,可以独自优化该结构域,这样可最大限度的扩大这项RNAi技术的应用范畴,对更多的基因起作用。具有更广阔的临床应用前景。

 

U1接头具有高度的活性,同时还能作为协同技术与RNAi一起发挥功效。

 

研究者认为,U1接头的技术不仅能用于研究基因的功能还能用于研究基因沉默的靶位设计。

(生物通 小茜)

 

原文检索:A New Gene Silencing Platform -- Silence Is Golden

 

索取Invitrogen公司RNAi产品资料


 A team of researchers led by Rutgers' Samuel Gunderson has developed a novel gene silencing platform with very significant improvements over existing RNAi approaches. This may enable the development and discovery of a new class of drugs to treat a wide array of diseases. Critical to the technology is the approach this team took to specifically target RNA biosynthesis.

The research findings are reported in the journal Nature Biotechnology, published online in the February 8th issue.

Gunderson, an associate professor in the Department of Molecular Biology and Biochemistry at Rutgers, The State University of New Jersey, has created highly efficient gene silencing agents that function via a novel mechanism of action. The agents are single-stranded oligonucleotides, called U1 Adaptors, that have dual, and independent, functions. First is a target-gene binding domain that can be tailored to any gene. The second domain inhibits mRNA maturation by binding U1 snRNP, a component of the cellular splicing apparatus.

By combining both capabilities in the same molecule, the U1 Adaptor can inhibit the pre-mRNA maturation step of polyA tail addition in a gene specific manner. Further, the domains of the oligonucleotide are independent so transcript binding and U1 snRNP binding can be independently optimized and adapted to a wide array of genes associated with disease.

"The U1 Adaptor platform expands on early technologies that used 5'-end-mutated U1 snRNA," Gunderson explained. "The U1 Adaptor is an oligonucleotide version of this older method and instead targets the 3' end processing step. U1 Adaptors have high activity when used alone and are synergistic when used in combination with RNAi." Gunderson went on to say that the range of possible targets is very broad due to the mechanism of action in which inhibition occurs during the biosynthesis of mRNA at the near universal 3' end processing step. Perhaps the most interesting aspect of this technology is that U1 Adaptors can possibly inhibit genes that do not respond to current RNAi methods.

The applications of U1 Adaptors expand on those currently available using standard RNAi approaches. They can be used as a research tool to determine gene function and to validate gene targets. Gene silencing molecules also have potential prophylactic and therapeutic applications based upon ongoing clinical trials using RNAi and traditional antisense approaches. For some genes that cause disease, these other approaches may not be effective enough and U1 Adaptors may provide a novel solution.'

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