Published March 31, 2021 | Version v1
Journal article Open

Gene Editing of Hematopoietic Stem Cells: Hopes and Hurdles Toward Clinical Translation

  • 1. San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy - PhD course in Molecular Medicine, Vita-Salute San Raffele University, Milan, Italy
  • 2. San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy - PhD course in Molecular Medicine, Vita-Salute San Raffele University, Milan, Italy - Pediatric Immunohematology and Bone Marrow Transplantation Unit, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milan, Italy
  • 3. San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy - PhD Program in Translational and Molecular Medicine (DIMET), Milano-Bicocca University, Monza, Italy
  • 4. San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy - Institute of Genetic and Biomedical Research Milan Unit, National Research Council, Milan, Italy
  • 5. San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy
  • 6. Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, United States - Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, United States - Harvard Stem Cell Institute, Cambridge, MA, United States - Department of Pediatrics, Harvard Medical School, Boston, MA, United States

Description

In the field of hematology, gene therapies based on integrating vectors have reached outstanding results for a number of human diseases. With the advent of novel programmable nucleases, such as CRISPR/Cas9, it has been possible to expand the applications of gene therapy beyond semi-random gene addition to site-specific modification of the genome, holding the promise for safer genetic manipulation. Here we review the state of the art of ex vivo gene editing with programmable nucleases in human hematopoietic stem and progenitor cells (HSPCs). We highlight the potential advantages and the current challenges toward safe and effective clinical translation of gene editing for the treatment of hematological diseases.

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Funding

UPGRADE – Unlocking Precision Gene Therapy 825825
European Commission