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Targeted cleavage of RNA using eukaryotic ribonucl

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专利名称:Targeted cleavage of RNA using eukaryotic

ribonuclease P and external guide sequence

发明人:Yan Yuan,Cecilia Guerrier-Takada,Sidney

Altman,Fenyong Liu

申请号:US08/215082申请日:19940318公开号:US05728521A公开日:19980317

摘要:It has been discovered that any RNA can be targeted for cleavage by RNAase Pfrom eukaryotic cells, for example, human RNAase P, using a suitably designed

oligoribonucleotide (\"external guide sequence\RNA, thereby creating a substrate for cleavage by RNAase P in vitro. The EGS hydrogenbonds to the targeted RNA to form a partial tRNA like structure including the aminoacylacceptor stem, the T stem and loop, and part of the D stem. The most efficient EGS withhuman RNAase P is the EGS in which the anticodon stem and loop was deleted.Modifications can also be made within the T- loop. Methods are also disclosed to

randomly select and to express a suitable EGS in vivo to make a selected RNA a target forcleavage by the host cell RNAase P, thus preventing expression of the function of thetarget RNA. The methods and compositions should be useful to prevent the expressionof disease- causing genes in vivo.

申请人:YALE UNIVERSITY

代理机构:Arnall Golden & Gregory, LLP

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