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Publication : DNA aptamers block L-selectin function in vivo. Inhibition of human lymphocyte trafficking in SCID mice.

First Author  Hicke BJ Year  1996
Journal  J Clin Invest Volume  98
Issue  12 Pages  2688-92
PubMed ID  8981912 Mgi Jnum  J:37235
Mgi Id  MGI:84637 Doi  10.1172/JCI119092
Citation  Hicke BJ, et al. (1996) DNA aptamers block L-selectin function in vivo. Inhibition of human lymphocyte trafficking in SCID mice. J Clin Invest 98(12):2688-92
abstractText  Selectins participate in the initial events leading to leukocyte extravasation from the blood into tissues. Thus the selectins have generated much interest as targets for antiinflammatory agents. Therapeutic molecules based on the monomeric carbohydrate ligand sialyl Lewis X (SLe(X)) have low affinities and are not specific for a given selectin. Using SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technology, we have generated aptamers specific for L-selectin that require divalent cations for binding and have low nanomolar affinity. In vitro, the deoxyoligonucleotides inhibit L-selectin binding to immobilized SLe(X) in static assays and inhibit L-selectin-mediated rolling of human lymphocytes and neutrophils on cytokine-activated endothelial cells in flow-based assays. These aptamers also block L-selectin-dependent lymphocyte trafficking in vivo, indicating their potential utility as therapeutics.
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