What are you looking for?

Karyn O’Neil is the Chief Scientific Officer and Co–Founder at Aro Biotherapeutics. She is a co-inventor on the Centyrin patents and has led the team focused on advancing the Centyrin targeting platform since its inception. At Aro, Karyn’s team is applying protein engineering, nucleic acid chemistry and chemical conjugation technologies to enable Centyrin – mediated intracellular delivery of nucleic acid cargos in a tissue specific manner.  Early in 2026, the Aro team completed a Phase 1b trial in late onset Pompe Disease demonstrating the utility of the Centyrin-siRNA platform for tissue targeted siRNA delivery.  The team has now expanded pre-clinical validation of the platform for delivery to immune cells for autoimmune diseases. Karyn received her PhD from the University of Pennsylvania where she focused on protein engineering and protein biophysics.   

Despite recent progress on oligonucleotide therapeutics for liver and muscle diseases, little progress has been made on delivery of oligonucleotides to other tissues.  Immune cells, especially dendritic cells and macrophages, represent a rich source of targets for autoimmune diseases.   The ability to specifically target and deliver siRNA to macrophages and dendritic cells to regulate gene expression upstream of target expression would provide novel opportunities for therapies in immune mediated disorders.   

Aro has clinically validated CD71 (TrfR1) Centyrins, small FN3 based protein domains, for targeted delivery of siRNA to muscle. In addition, we recently created next generation FN3 based libraries with an expanded repertoire of potential binders to select ideal targeting proteins for extra-hepatic siRNA delivery. Here we present the utility of CD71 Centyrins or novel CD206 (mannose receptor) binders for delivery of siRNAs into immune cells.  We demonstrate efficient mRNA knockdown using CD71 Centyrins conjugated to AHA1 siRNA in muscle cells, dendritic cells and macrophages while CD206 binders efficiently knock down mRNA in dendritic cells and macrophages with no activity in muscle. Together, this work supports Centyrin targeted RNAi as a modular strategy to address genetically complex autoimmune diseases.