Selective removal of soluble FLT-1 using a high-affinity DNA aptamer for potential apheresis treatment of preeclampsia

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that has been associated with elevated levels of soluble fms-like tyrosine kinase-1 (sFLT-1), which is thought to contribute to impaired angiogenesis by binding and neutralizing angiogenic factors such as Vascular Endothelial Growth Factor (VEGF) and Placental Growth Factor (PlGF). Selective removal of sFLT-1 from the maternal circulation is being explored as a potential therapeutic approach for PE. In this study, we developed TXB-0080, a high-affinity DNA aptamer containing two distinct artificial bases (Xenoligo platform), which binds sFLT-1 with an affinity of KD = 0.084 ± 0.023 nM. TXB-0080 was immobilized onto Sepharose beads to construct an apheresis model that efficiently and specifically removed sFLT-1 from serum. The aptamer-conjugated beads exhibited stability against autoclaving and compatibility with clinical anticoagulants. Notably, it did not bind free PlGF but effectively captured sFLT-1 without interfering with its interaction with ligands. These findings support the feasibility of aptamer-based apheresis as a novel and targeted strategy to address sFLT-1–associated pathology in PE.