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Genome editing

Gene correction for sickle cell disease hits its prime

Nature Biomedical Engineering volume 7, pages 605–606 (2023)Cite this article

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Prime editing can efficiently rewrite the genetic mutation causing sickle cell disease, in haematopoietic stem cells from patients.

Therapeutic genome editing of haematopoietic stem cells (HSCs) may permanently remedy sickle cell disease (SCD) and other severe blood disorders. SCD is an autosomal recessive genetic disorder caused by an A·T-to-T·A transversion (the E6V mutation) at codon 6 in the HBB gene, which produces the adult haemoglobin subunit β-globin. The same single base-pair change affects millions of individuals around the world. Mutant β-globin polymerizes within red blood cells, resulting in the characteristic sickle shape of the cells and initiating haemolysis, microvascular occlusions, inflammation and organ damage. As the CRISPR toolkit has been expanding, substantial efforts have been dedicated to the development of efficient and sufficiently safe methods for the editing of HSCs ex vivo. Now reporting in Nature Biomedical Engineering, David Liu, Jonathan Yen and colleagues1 show that ex vivo prime editing can correct the HBBE6V mutation at therapeutically relevant frequencies in HSCs from patients. The findings support the future development of prime editing for the treatment of SCD1.

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Fig. 1: Prime editing at the β-globin gene locus corrects the HBBE6V mutation in human HSCs.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Boston Children’s Hospital, Boston, MA, USA

    Sébastien Levesque & Daniel E. Bauer

  2. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Sébastien Levesque & Daniel E. Bauer

  3. Harvard Stem Cell Institute, Cambridge, MA, USA

    Sébastien Levesque & Daniel E. Bauer

  4. Broad Institute, Cambridge, MA, USA

    Sébastien Levesque & Daniel E. Bauer

  5. Department of Pediatrics, Harvard Medical School, Boston, MA, USA

    Sébastien Levesque & Daniel E. Bauer

Authors
  1. Sébastien Levesque
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  2. Daniel E. Bauer
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Correspondence to Daniel E. Bauer.

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The authors declare no competing interests.

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Levesque, S., Bauer, D.E. Gene correction for sickle cell disease hits its prime. Nat. Biomed. Eng 7, 605–606 (2023). https://doi.org/10.1038/s41551-023-01040-2

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