Abstract
The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system
has revolutionized the gene editing field, making it possible to interrupt, insert
or replace a sequence of interest with high precision in the human genome. Its easy
design and wide applicability open up a variety of therapeutic alternatives for the
treatment of genetic diseases. Indeed, very promising approaches for the correction
of hematological disorders have been developed in the recent years, based on the self-renewal
and multipotent differentiation properties of hematopoietic stem and progenitor cells,
which make this cell subset the ideal target for gene therapy purposes. This technology
has been applied in different congenital blood disorders, such as primary immunodeficiencies,
X-linked severe combined immunodeficiency, X-linked chronic granulomatous disease
or Wiskott–Aldrich syndrome, and inherited bone marrow failure syndromes, such as
Fanconi anemia, congenital amegakaryocytic thrombocytopenia or severe congenital neutropenia.
Furthermore, CRISPR/Cas9-based gene editing has been implemented successfully as a
novel therapy for cancer immunotherapy, by the development of promising strategies
such as the use of oncolytic viruses or adoptive cellular therapy to the chimeric
antigen receptor–T-cell therapy. Therefore, considering the variety of genes and mutations
affected, we can take advantage of the different DNA repair mechanisms by CRISPR/Cas9
in different manners, from homology-directed repair to non-homologous-end-joining
to the latest emerging technologies such as base and prime editing. Although the delivery
systems into hematopoietic stem and progenitor cells are still the bottleneck of this
technology, some of the advances in genome editing shown in this review have already
reached a clinical stage and show very promising preliminary results.
Key Words
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Article info
Publication history
Published online: January 05, 2023
Accepted:
November 30,
2022
Received:
December 15,
2021
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
