Next-Generation Percutaneous Catheter–Based Closed-Loop Perfusion Concept Enables High-Precision Organ Delivery of Advanced Therapies

Safe and efficient in vivo delivery of advanced therapies (ATs) remains a major challenge hindering their path to clinical adoption. We present a novel, fully percutaneous, catheter-based locoregional perfusion (LRP) system for targeted delivery of ATs, minimizing systemic exposure. Using principles from extracorporeal membrane oxygenation and cardiovascular perfusion, we developed and validated the LRP concept in porcine models, focusing on the kidney as a clinically relevant target. Custom catheter prototypes enabled safe, isolated perfusion of the kidney. Using adeno-associated viruses (AAVs) as model cargos, LRP achieved up to 69,000-fold higher vector retention within the LRP circulation than systemic circulation, and significantly reduced delivery to off-target organs such as the liver and spleen. AAV5 showed the highest transduction efficiency, with up to 75-fold greater gene expression. These findings demonstrate the feasibility, safety, and precision of LRP for organ-specific AT delivery while preventing plausible off-target toxicity. It may therefore represent a unique platform for next-generation delivery of AT and potentially beyond, including other therapeutic agents such as pharmaco- or chemotherapy to the target-organ.