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Gene Editing in Human Haematopoietic Stem Cells for the Treatment of Primary Immunodeficiencies

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Abstract

In recent years, gene-editing technologies have revolutionised precision medicine, and human trials of this technology have been reported in cell-based cancer therapies and other genetic disorders. The same techniques have the potential to reverse mutations in monogenic primary immunodeficiencies (PIDs), and transplantation of edited haematopoietic stem cells may provide a functional cure for these diseases. In this review, we discuss the methods of gene editing being explored and describe progress made so far with several PIDs. We also detail the remaining challenges, how to confidently detect off-target effects and chromosomal abnormalities in a timely manner, how to obtain long-term benefits, and how to achieve physiological levels of expression of the therapeutic gene. With advances in gene editing, we envisage a robust clinical translation of this technology in the coming decade.

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Correspondence to Sameer Bahal or Giorgia Santilli.

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Sameer Bahal, Klesti Karaxhuku and Giorgia Santilli declare that they have no conflicts of interest.

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Bahal, S., Karaxhuku, K. & Santilli, G. Gene Editing in Human Haematopoietic Stem Cells for the Treatment of Primary Immunodeficiencies. Mol Diagn Ther 27, 15–28 (2023). https://doi.org/10.1007/s40291-022-00618-x

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