A HAMMERHEAD RIBOZYME THAT CLEAVES PERFORIN AND FAS-LIGAND RNAS IN-VITRO

Polyfunctional ribozymes targeting more than one RNA might be ideal fo r 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 mo del is due to the action of two proteins responsible for different lyt ic pathways: perforin and fas-ligand. We have created a bifunctional r ibozyme fusing two antiperforin and antifas-ligand hammerhead ribozyme s with a stretch of CA dinucleotides. This bifunctional ribozyme is ab le 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. (C) 1996 Academic Press, Inc.