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The generation and characterisation of antagonist RNA aptamers to MCP‐1
Author(s) -
Rhodes Andrew,
Smithers Nick,
Chapman Trevor,
Parsons Sarah,
Rees Stephen
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02895-2
Subject(s) - aptamer , monocyte , in vitro , function (biology) , chemotaxis , rna , chemistry , inflammation , selex aptamer technique , computational biology , receptor , biology , pharmacology , microbiology and biotechnology , immunology , systematic evolution of ligands by exponential enrichment , biochemistry , gene
Monocyte chemoattractant protein‐1 (MCP‐1) has been implicated as a powerful pro‐inflammatory mediator and may represent a potentially important, therapeutic opportunity for treatment of inflammatory disease and atherosclerosis. To further investigate the role of MCP‐1 in inflammatory disorders we have isolated a series of RNA aptamers that bind specifically to mouse MCP‐1. The highest affinity aptamers, designated ADR7 and ADR22, have been functionally characterised in vitro and in cell based assays. ADR7 and ADR22 have an affinity of 180 pM and 370 pM respectively for mouse MCP‐1, they can antagonise MCP‐1 binding to heparin and specifically antagonise MCP‐1 induced 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, demonstrating the high level of specificity of these aptamers and that the aptamers recognise MCP‐1 in different ways. The aptamers may be used as a tool to further investigate the role of MCP‐1 in inflammatory disorders and may also have a role as a therapeutic agent.