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Editing human hematopoietic stem cells: advances and challenges

  • Senthil Velan Bhoopalan
    Affiliations
    Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
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  • Jonathan S. Yen
    Affiliations
    Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
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  • Rachel M. Levine
    Affiliations
    Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
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  • Akshay Sharma
    Correspondence
    Correspondence: Akshay Sharma, MBBS, Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS1130, Memphis, Tennessee 38105, USA.
    Affiliations
    Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
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Published:September 17, 2022DOI:https://doi.org/10.1016/j.jcyt.2022.08.003

      Abstract

      Genome editing of hematopoietic stem and progenitor cells is being developed for the treatment of several inherited disorders of the hematopoietic system. The adaptation of CRISPR-Cas9-based technologies to make precise changes to the genome, and developments in altering the specificity and efficiency, and improving the delivery of nucleases to target cells have led to several breakthroughs. Many clinical trials are ongoing, and several pre-clinical models have been reported that would allow these genetic therapies to one day offer a potential cure to patients with diseases where limited options currently exist. However, there remain several challenges with respect to establishing safety, expanding accessibility and improving the manufacturing processes of these therapeutic products. This review focuses on some of the recent advances in the field of genome editing of hematopoietic stem and progenitor cells and illustrates the ongoing challenges.

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