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Updated: Feb 18, 2026

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
Published on: May 9, 2025
Gene therapy for primary immunodeficiencies
Christine Rivat1, Giorgia Santilli, H Bobby Gaspar
1UCL Institute of Child Health, Centre for Immunodeficiency, London WCIN 1EH, United Kingdom.
Abstract:
For over 40 years, primary immunodeficiencies (PIDs) have featured prominently in the development and refinement of human allogeneic hematopoietic stem cell transplantation. More recently, ex vivo somatic gene therapy using autologous cells has provided remarkable evidence of clinical efficacy in patients without HLA-matched stem cell donors and in whom toxicity of allogeneic procedures is likely to be high. Together with improved preclinical models, a wealth of information has accumulated that has allowed development of safer, more sophisticated technologies and protocols that are applicable to a much broader range of diseases. In this review we summarize the status of these gene therapy trials and discuss the emerging application of similar strategies to other PIDs.
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