Advancements in Omics and Breakthrough Gene Therapies: A Glimpse into the Future of Peripheral Artery Disease

Phillip G Brennan; Lucas Mota; Tarek Aridi; Nyah Patel; Patric Liang; Christiane Ferran

doi:10.1016/j.avsg.2024.01.031

Advancements in Omics and Breakthrough Gene Therapies: A Glimpse into the Future of Peripheral Artery Disease

Ann Vasc Surg. 2024 Apr 4:S0890-5096(24)00156-0. doi: 10.1016/j.avsg.2024.01.031. Online ahead of print.

Authors

Phillip G Brennan¹, Lucas Mota¹, Tarek Aridi², Nyah Patel¹, Patric Liang¹, Christiane Ferran³

Affiliations

¹ Division of Vascular and Endovascular Surgery, and Center for Vascular Biology Research, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
² Division of Vascular and Endovascular Surgery, and Center for Vascular Biology Research, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.
³ Division of Vascular and Endovascular Surgery, and Center for Vascular Biology Research, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Division of Nephrology and the Transplant Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Electronic address: cferran@bidmc.harvard.edu.

PMID: 38582204
DOI: 10.1016/j.avsg.2024.01.031

Abstract

Peripheral artery disease (PAD), a highly prevalent global disease, associates with significant morbidity and mortality in affected patients. Despite progress in endovascular and open revascularization techniques for advanced PAD, these interventions grapple with elevated rates of arterial restenosis and vein graft failure attributed to intimal hyperplasia (IH). Novel multiomics technologies, coupled with sophisticated analyses tools recently powered by advances in artificial intelligence, have enabled the study of atherosclerosis and IH with unprecedented single-cell and spatial precision. Numerous studies have pinpointed gene hubs regulating pivotal atherogenic and atheroprotective signaling pathways as potential therapeutic candidates. Leveraging advancements in viral and nonviral gene therapy (GT) platforms, gene editing technologies, and cutting-edge biomaterial reservoirs for delivery uniquely positions us to develop safe, efficient, and targeted GTs for PAD-related diseases. Gene therapies appear particularly fitting for ex vivo genetic engineering of IH-resistant vein grafts. This manuscript highlights currently available state-of-the-art multiomics approaches, explores promising GT-based candidates, and details GT delivery modalities employed by our laboratory and others to thwart mid-term vein graft failure caused by IH, as well as other PAD-related conditions. The potential clinical translation of these targeted GTs holds the promise to revolutionize PAD treatment, thereby enhancing patients' quality of life and life expectancy.