Next-Generation Percutaneous Catheter–Based Closed-Loop Perfusion Concept Enables High-Precision Organ Delivery of Advanced Therapies
OPEN ACCESS
Loading...
Author / Producer
Date
2025-12
Publication Type
Journal Article
ETH Bibliography
yes
OPEN ACCESS
Data
Abstract
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.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
10 (12)
Pages / Article No.
101409
Publisher
Elsevier
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
adeno-associated virus; delivery; gene therapy; kidney isolation; loco-regional perfusion; transcatheter