Platelet-targeted gene therapy induces immune tolerance in hemophilia and beyond. J Thromb Haemost 2024 Jan;22(1):23-34
Date
08/10/2023Pubmed ID
37558132Pubmed Central ID
PMC11249137DOI
10.1016/j.jtha.2023.07.025Scopus ID
2-s2.0-85169506503 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
Blood platelets have unique storage and delivery capabilities. Platelets play fundamental roles in hemostasis, inflammatory reactions, and immune responses. Beyond their functions, platelets have been used as a target for gene therapy. Platelet-targeted gene therapy aims to deliver a sustained expression of neo-protein in vivo by genetically modifying the target cells, resulting in a cure for the disease. Even though there has been substantial progress in the field of gene therapy, the potential development of immune responses to transgene products or vectors remains a significant concern. Of note, multiple preclinical studies using platelet-specific lentiviral gene delivery to hematopoietic stem cells in hemophilia have demonstrated promising results with therapeutic levels of neo-protein that rescue the hemorrhagic bleeding phenotype and induce antigen-specific immune tolerance. Further studies using ovalbumin as a surrogate protein for platelet gene therapy have shown robust antigen-specific immune tolerance induced via peripheral clonal deletions of antigen-specific CD4- and CD8-T effector cells and induction of antigen-specific regulatory T (Treg) cells. This review discusses platelet-targeted gene therapy, focusing on immune tolerance induction.
Author List
Kumar S, Schroeder JA, Shi QAuthor
Qizhen Shi MD, PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Blood PlateletsFactor VIII
Genetic Therapy
Hemophilia A
Hemostasis
Humans
Immune Tolerance
