ORIGINAL RESEARCH

Transpl Int

Volume 38 - 2025 | doi: 10.3389/ti.2025.13971

This article is part of the Special IssueCurrent developments in artificial organs and engineered ex-situ perfused organsView all 13 articles

Delivery of a Muscle-Targeted Adeno-Associated Vector via Ex Vivo Normothermic Perfusion is Efficient, Durable, and Safe in a Preclinical Porcine Heart Transplant Model

Krish C DewanKrish C Dewan1*Jeng-Wei ChenJeng-Wei Chen1,2Alejandro A LoboAlejandro A Lobo1Ryan T GrossRyan T Gross1Chunbo WangChunbo Wang1Karla G RiveraKarla G Rivera1Keely Dieplin TranKeely Dieplin Tran1Smith NgeveSmith Ngeve1Violet G JohnstonViolet G Johnston1David WendellDavid Wendell3Carolyn K GlassCarolyn K Glass4Amy EvansAmy Evans5Sam HoSam Ho6Paul LezbergPaul Lezberg7Widler CasyWidler Casy8Marla BazileMarla Bazile8Kruti PatelKruti Patel8Adam S CockrellAdam S Cockrell8Carmelo A MilanoCarmelo A Milano1Dawn E BowlesDawn E Bowles1
  • 1Department of Surgery, Duke University Medical Center, Duke University, Durham, United States
  • 2Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
  • 3Duke Cardiovascular Magnetic Resonance Center, Duke University Medical Center, Duke University, Durham, United States
  • 4Department of Pathology, Duke University Medical Center, Duke University, Durham, United States
  • 5Perfusion Services, Duke University Medical Center, Duke University, Durham, United States
  • 6Gift of Hope Organ and Tissue Donor Network, Itasca, IL, United States
  • 7TransMedics, Inc., Andover, MA, United States
  • 8Solid Biosciences Inc., Charlestown, Massachusetts, United States

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Normothermic ex-vivo organ perfusion (EVP) systems not only provide a physiological environment that preserves donor organ function outside the body but may also serve as platforms for ex-vivo organ modification via gene therapy. In this study, we demonstrated that a rationally designed muscle-tropic recombinant AAV, AAV-SLB101, delivered to the donor heart during brief normothermic EVP achieves durable cardiac transgene expression out to 90 and 120 days post-transplant in a porcine preclinical model. Moreover, transgene expression was detectable as early as 48 hours post-transplant. Histological and MRI analyses of the donor myocardium showed no functional or structural impact on the allograft and no off-target gene expression in the recipient. This work will serve as a critical foundation to inform translational studies with therapeutic transgenes to improve allo-, xeno-, and auto-heart transplant outcomes.

Keywords: Adeno-associated virus vector, gene therapy, heart transplantation, ex vivo heart preservation, transgene durability

Received: 22 Oct 2024; Accepted: 20 May 2025.

Copyright: © 2025 Dewan, Chen, Lobo, Gross, Wang, Rivera, Tran, Ngeve, Johnston, Wendell, Glass, Evans, Ho, Lezberg, Casy, Bazile, Patel, Cockrell, Milano and Bowles. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Krish C Dewan, Department of Surgery, Duke University Medical Center, Duke University, Durham, United States

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material