[Specific inhibition of anti-DNA antibody production by an anti-DH ribozyme]

In order to develop a new therapy for systemic lupus erythematosus, we designed a ribozyme (catalytic RNA) to specifically cleave the mRNA of anti-DNA-responsible VH genes and tested for their ability to regulate the production of autoantibody by human B cell clone O-81 expressing nephritogenic idiotypes. Based on a preliminary antisense experiments for O-81 VH gene, we determined the regions in O-81 mRNA, which would be the target site for the cleavege. The O-81 ribozyme specifically inhibited the production of anti-DNA antibody by O-81 cones. For application to clinical state, nuclease-resistance ribozyme has been expected. These results indicate to introduce ribozymes as a new method of therapy in autoimmune diseases.