Preformed Ribozymes: Strategies for Design and In Vivo Application as Anticytokine Agents

Inflammation and tissue injury are characterized by a massive infiltration of mononuclear cells responsible for the production of a variety of cytokines that alter the biosynthetic repertoire of the connective tissue cells (1 ,2 ). Recently, experiments in animal models of autoimmunity have demonstrated that the over- or local-expression of a single proinflammatory cytokine can induce certain autoimnnune disorders (3 –7 ). These results highlight the involvement of cytokines in autoimmune diseases and illustrate the imperative necessity for developing new anticytokine agents that can be used to block or dissect the function of genes involved in the inflammatory processes. Three major approaches have been used to downregulate the expression of genes involved in disease. One approach is the use of antibodies that work at the protein level (8 ). The second approach is antisense DNA or RNA (9 ) and the third approach is the use of ribozymes (for review see ref. 10 ). For therapeutic application, cleaving RNAs by specific ribozymes seems to be more feasible than the two other approaches.