The generation and characterization of antagonist RNA aptamers to human oncostatin M

Oncostatin M (OSM) is a multifunctional member of the interleukin-6 cytokin e family. OSM has been implicated as a powerful proinflammatory mediator an d may represent a potentially important, novel therapeutic opportunity for treatment of established rheumatoid arthritis. To further investigate the r ole of OSM in inflammatory disorders, we have isolated a series of RNA apta mers that bind specifically to human OSM, The highest affinity aptamer, des ignated ADR58, has been characterized in a series of in vitro and cell base d assays. ADR58 has an affinity of 7 nm for human OSM, and it can antagoniz e OSM binding to the gp130 receptor and specifically antagonize OSM mediate d signaling. The aptamer has been truncated in length to 33 bases, all pyri midine positions are substituted with 2' fluorine, and 14 of 18 purine posi tions have been substituted with 2' O-methyl to increase stability toward n ucleases, This truncated, modified form of ADR58 retains complete affinity and functional activity for OSM, This aptamer may be used as a tool to furt her investigate the role of OSM in inflammatory disorders and may also have role as a therapeutic agent.