The generation and characterisation of antagonist RNA aptamers to MCP-1

Monocyte chemoattractant protein-1 (MCP-1) has been implicated as a powerfu l pro-inflammatory mediator and may represent a potentially important, ther apeutic opportunity for treatment of inflammatory disease and atheroscleros is. To further investigate the role of MCP-1 in inflammatory disorders we h ave isolated a series of RNA aptamers that bind specifically to mouse MCP-1 . The highest affinity aptamers, designated ADR7 and ADR22, have been funct ionally characterised in vitro and in cell based assays. ADR7 and ADR22 hav e an affinity of 180 pM and 370 pM respectively for mouse MCP-1, they can a ntagonise MCP-1 binding to heparin and specifically antagonise MCP-1 induce d chemotaxis in a cell based assay. An interesting feature of ADR22 but not ADR7 is that it is capable of antagonising the function of human MCP-1, de monstrating the high level of specificity of these aptamers and that the ap tamers recognise MCP-1 in different ways. The aptamers may be used as a too l to further investigate the role of MCP-1 in inflammatory disorders and ma y also have a role as a therapeutic agent. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserv ed.