Computationally Designed De Novo sFlt1 Minibinders as a Low-Cost Treatment for Preeclampsia

Christian Richardson of RiffTX in the U.S. will develop minibinder proteins targeting sFlt1 as a candidate preeclampsia treatment and a drug manufacturing process suitable for low- and middle-income countries (LMICs). Preeclampsia is a placental disease whose pathologies converge on elevated levels of sFlt1. The project will generate small, high-affinity binding proteins (minibinders) to inhibit sFLT1 function along with minibinders for human serum albumin (HSA) and for neonatal Fc receptor (FcRn) to maintain a long drug half-life in circulation. A manufacturing process will be developed to produce a high-quality drug while ensuring the cost and complexity of the process is suitable for implementation in LMICs. Drug candidates will be tested for an extended half-life using transgenic mice expressing HAS and human FcRN, and they will be tested for restoration of blood pressure and kidney function levels normal for pregnant rats using a rat model of preeclampsia.