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Blocking an ion channel with a bioengineered peptibody

Bojjibabu Chidipi

Novel ion channels blocking modalities are needed for the development of the next generation of safer and more effective antiarrhythmic pharmacotherapies. As a proof of concept, we engineered and produced an ion channel blocking peptibody, that targets the acetylcholine activated inward rectifier potassium current (IKACh). The peptibody was engineered as a fusion protein between the human IgG1 Fc fragment fusion protein and TertiapinQ, a 21 amino acid European honey bee venom that inhibits IKACh. We tested the hypothesis that the peptibody is a more potent blocker of IKACh compared to TertiapinQ. Methods: We used patch clamp, multiple electrode arrays (MEA) and whole animal electrophysiology to evaluate the peptibodyÃ