简介：Humantumornecrosisfactorα(hTNFα),apleiotropiccytokinewithactivitiesrangingfromhostdefensemechanismsininfectionandinjurytoseveretoxicityinsepticshockorotherrelateddiseases,isapromisingtargetfordrugscreening.UsingtheSELEX(systematicevolutionofligandsbyexponentialenrichment)process,weisolatedoligonucleotideligands(aptamers)withhighaffinitiesforhTNFα.Aptamerswereselectedfromastartingpoolof40randomizedsequencescomposedofabout1015RNAmolecules.RepresentativeaptamersweretruncatedtotheminimallengthwithhighaffinityforhTNFαandwerefurthermodifiedbyreplacementof2'-OHwith2'-Fand2'-NH2atallribopurinepositions.ThesemodifiedRNAaptamerswereresistanttonuclease.ThespecificityoftheseaptamersforhTNFαwasconfirmed,andtheiractivitytoinhibitthecytotoxicityofhTNFαonmouseL929cellswasdetermined.Resultsdemonstratedthatfour2'-NH2-modifiedaptamersboundtohTNFαwithhighaffinityandblockedthebindingofhTNFαtoitsreceptor,thusprotectingtheL929cellsfromthecytotoxicityofhTNFα.OligonucleotideaptamersdescribedherearepotentialtherapeuticsanddiagnosticsforhTNFc-relateddiseases.