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RNAi技术在基因组学中的应用

发布时间: 2017-06-12  点击次数: 574次

国外越来越多的研究单位和公司都采用rnai技术平台来筛选药物的靶点或疾病的靶点。目前在模式生物中取得了很大进展,如果蝇,斑马鱼,线虫等,今后的工作重点则是在高等的哺乳动物,尤其是小鼠等,这种高通量的筛选方法是今后发展的重要趋势和手段。 

Christophe Echeverri thinks big with sirnas. 

RNA interference (RNAi) is a powerful method of gene silencing using double-stranded RNA, which is converted to small inhibitory RNA (siRNA) as the active agent. siRNAs are now hot RNAi技术在基因组学中的应用property as reagents for knocking down gene expression in target identification and validation assays, and as possible therapeutics for silencing genes associated with disease. 

According to Christophe Echeverri, chief executive and scientific officer of Cenix BioScience in Dresden, Germany, high-throughput RNAi is the most exciting recent development in target discovery and validation. "The key advance here is the development of genome-wide libraries of siRNAs to enable genome-wide screens in human cells," he says. "It offers the most direct, cost-efficient way to get from gene sequence to gene function at a genomic scale." As part of its drug-discovery and target-validation programmes, Cenix has designed siRNAs against more than 98% of the human, mouse and rat genes identified by the genome-sequencing projects; the siRNAs themselves, for all these genes listed in the RefSeq database, are available to order through Ambion of Austin, Texas, which also offers an off-the-shelf library of nearly 600 kinase siRNAs made to the Cenix RNAi技术在基因组学中的应用designs.

The siRNA drug-development company Atugen in Berlin, Germany, also develops siRNAs as both reagents for target identification and validation and as potential therapeutics. Atugen’s technology platform for target identification uses various messenger RNA knockdown techniques, including proprietary siRNAs chemically modified for increased stability, and a proprietary antisense method called GENEblocs. "These are used in combination with proprietary liposomal formulations to elucidate gene function in specialized cellular assays and animal models," says Klaus Giese, chief scientific officer at Atugen. "Matching results found with siRNA and Geneblocs will substantially increase the probability that an observed phenotype is clinically relevant." 

RNAi allows more questions to be asked of mammalian cells than ever before. "The ability of RNAi to allow the ’yeastification’ of mammalian cells in terms of genetics is very exciting," says Kevin Fitzgerald, group leader of applied genomics at Bristol-Myers Squibb in New York. "With RNAi we can now begin to approach the genetics of tumour-suppressor genes in a whole new way. We have known that the loss of these genes is very important in the development of cancer for years, but we have been unable to develop specific drugs directed at them. With RNAi we can now ask whether there are any druggable targets in the genome that will lead to the death of cells missing tumour suppressors but leave normal cells alone. This is a question that in mammalian cells we simply could not have asked a few years ago."