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RNAi技術(shù)在基因組學(xué)中的應(yīng)用
點(diǎn)擊次數(shù)：662 發(fā)布時(shí)間：2017-6-12
國(guó)外越來越多的研究單位和公司都采用rnai技術(shù)平臺(tái)來篩選藥物的靶點(diǎn)或疾病的靶點(diǎn)。目前在模式生物中取得了很大進(jìn)展，如果蠅，斑馬魚，線蟲等，今后的工作重點(diǎn)則是在高等的哺乳動(dòng)物，尤其是小鼠等，這種高通量的篩選方法是今后發(fā)展的重要趨勢(shì)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技術(shù)在基因組學(xué)中的應(yīng)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技術(shù)在基因組學(xué)中的應(yīng)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."