biostudies-literatureMachha VRMayo Clinic Comprehensive Hemophilia Treatment CenterNational Heart, Lung, and Blood InstituteNHLBI NIH HHSHealth Resources and Services AdministrationNational Institute of General Medical SciencesNIGMS NIH HHSugae021https://www.ebi.ac.uk/biostudies/studies/S-EPMC11664255biostudies-literatureUnknown1(4)The A1 domain in Von Willebrand Factor (VWF) initiates coagulation through binding to platelet glycoprotein GPIbα receptors. Von Willebrand Disease (VWD)-Mutations in A1 that either impair (type 2M) or enhance (type 2B) platelet adhesion to VWF can locally destabilize and even misfold the domain. We leveraged misfolding in the gain-of-function type 2B VWD phenotype as a target, distinct from the normal conformation. Two nuclease-resistant 2'-fluoropyrimidine RNA aptamers were selected to discriminate normal A1 domains from a type 2B V1314D A1 variant in a glycosylated A1A2A3 tri-domain VWF-fragment. Two aptamers, W9 and V1, were isolated that selectively recognize, bind, and inhibit the A1-GPIbα interaction with WT A1A2A3 and V1314D A1A2A3, respectively. These aptamers were tested against NAR molecular medicineConformation-specific RNA aptamers for phenotypic distinction between normal von Willebrand factor and type 2B von Willebrand disease.PMC11664255GM143949HL146508 to M.A.R01 HL146508R35 GM143949H30MC24052Moon-Tasson LSantiago-Davis AMachha VRTischer ATange JPruthi RKAuton MChen DMaher LJfalseConformation-specific RNA aptamers for phenotypic distinction between normal von Willebrand factor and type 2B von Willebrand disease.The A1 domain in Von Willebrand Factor (VWF) initiates coagulation through binding to platelet glycoprotein GPIbα receptors. Von Willebrand Disease (VWD)-Mutations in A1 that either impair (type 2M) or enhance (type 2B) platelet adhesion to VWF can locally destabilize and even misfold the domain. We leveraged misfolding in the gain-of-function type 2B VWD phenotype as a target, distinct from the normal conformation. Two nuclease-resistant 2'-fluoropyrimidine RNA aptamers were selected to discriminate normal A1 domains from a type 2B V1314D A1 variant in a glycosylated A1A2A3 tri-domain VWF-fragment. Two aptamers, W9 and V1, were isolated that selectively recognize, bind, and inhibit the A1-GPIbα interaction with WT A1A2A3 and V1314D A1A2A3, respectively. These aptamers were tested against 2024-01-01T00:00:00Z2024 Oct2026-04-07T21:22:12.168Z2025-04-04T13:41:45.596ZS-EPMC116642553971996810.1093/narmme/ugae021