Thrombotic Microangiopathy as an Emerging Complication of Viral Vector-Based Gene Therapy

Nora Schwotzer; Carine El Sissy; Isabelle Desguerre; Véronique Frémeaux-Bacchi; Laurent Servais; Fadi Fakhouri

doi:10.1016/j.ekir.2024.04.024

Thrombotic Microangiopathy as an Emerging Complication of Viral Vector-Based Gene Therapy

Kidney Int Rep. 2024 Apr 15;9(7):1995-2005. doi: 10.1016/j.ekir.2024.04.024. eCollection 2024 Jul.

Authors

Nora Schwotzer¹, Carine El Sissy^{2

3}, Isabelle Desguerre⁴, Véronique Frémeaux-Bacchi^{2

3}, Laurent Servais^{5

6}, Fadi Fakhouri¹

Affiliations

¹ Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
² Department of Immunology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
³ Paris University, Paris, France.
⁴ Paediatric Neurology Department, Necker Hospital, APHP Centre, Université Paris Cité, Paris, France.
⁵ MDUK Oxford Neuromuscular Center and NIHR Oxford Biomedical Research Center, University of Oxford, Oxford, UK.
⁶ Neuromuscular Center, Department of Pediatrics, University of Liege and University Hospital of Liege, Belgium.

Abstract

Gene therapy has brought tremendous hope for patients with severe life-threatening monogenic diseases. Although studies have shown the efficacy of gene therapy, serious adverse events have also emerged, including thrombotic microangiopathy (TMA) following viral vector-based gene therapy. In this review, we briefly summarize the concept of gene therapy, and the immune response triggered by viral vectors. We also discuss the incidence, presentation, and potential underlying mechanisms, including complement activation, of gene therapy-associated TMA. Further studies are needed to better define the pathogenesis of this severe complication of gene therapy, and the optimal measures to prevent it.

Keywords: complement; gene therapy; immune response; thrombotic microangiopathy.

Publication types

Review