A hammerhead ribozyme that cleaves perforin and fas-ligand RNAs in vitro.
Polyfunctional ribozymes targeting more than one RNA might be ideal for treatment of diseases caused by the expression of more than one mRNA. This is the case of Graft versus Host Disease, which in the mouse model is due to the action of two proteins responsible for different lytic pathways: perforin and fasligand. We have created a bifunctional ribozyme fusing two antiperforin and antifas-ligand hammerhead ribozymes with a stretch of CA dinucleotides. This bifunctional ribozyme is able to recognize and cleave in vitro perforin and fas-ligand mRNA in a specific and selective fashion, with a catalytic efficiency similar to that of its individual components.
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Diabetes Research Institute, University of Miami School of Medicine, Florida 33136, USA.
Ricordi
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Podack
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Pastori
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D000818:Animals; D001483:Base Sequence; D053222:Fas Ligand Protein; D006086:Graft vs Host Disease / Q000276:immunology / Q000503:physiopathology; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012323:RNA Processing, Post-Transcriptional; D016337:RNA, Catalytic / Q000096:biosynthesis / Q000378:metabolism*; D013379:Substrate Specificity; D019014:fas Receptor / Q000096:biosynthesis*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D052899:Pore Forming Cytotoxic Proteins; D016337:RNA, Catalytic; D019014:fas Receptor; D054353:Perforin