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The CRISPR-Cas System and Clinical Applications of CRISPR-Based Gene Editing in Hematology with a Focus on Inherited Germline Predisposition to Hematologic Malignancies

Overview
Journal Genes (Basel)
Publisher MDPI
Date 2024 Jul 27
PMID 39062641
Authors
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Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing has begun to transform the treatment landscape of genetic diseases. The history of the discovery of CRISPR/CRISPR-associated (Cas) proteins/single-guide RNA (sgRNA)-based gene editing since the first report of repetitive sequences of unknown significance in 1987 is fascinating, highly instructive, and inspiring for future advances in medicine. The recent approval of CRISPR-Cas9-based gene therapy to treat patients with severe sickle cell anemia and transfusion-dependent β-thalassemia has renewed hope for treating other hematologic diseases, including patients with a germline predisposition to hematologic malignancies, who would benefit greatly from the development of CRISPR-inspired gene therapies. The purpose of this paper is three-fold: first, a chronological description of the history of CRISPR-Cas9-sgRNA-based gene editing; second, a brief description of the current state of clinical research in hematologic diseases, including selected applications in treating hematologic diseases with CRISPR-based gene therapy, preceded by a brief description of the current tools being used in clinical genome editing; and third, a presentation of the current progress in gene therapies in inherited hematologic diseases and bone marrow failure syndromes, to hopefully stimulate efforts towards developing these therapies for patients with inherited bone marrow failure syndromes and other inherited conditions with a germline predisposition to hematologic malignancies.

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References
1.
East-Seletsky A, OConnell M, Knight S, Burstein D, Cate J, Tjian R . Two distinct RNase activities of CRISPR-C2c2 enable guide-RNA processing and RNA detection. Nature. 2016; 538(7624):270-273. PMC: 5576363. DOI: 10.1038/nature19802. View

2.
Lieber M . The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem. 2010; 79:181-211. PMC: 3079308. DOI: 10.1146/annurev.biochem.052308.093131. View

3.
Vissers L, van der Burg M, Lankester A, Smiers F, Bartels M, Mohseny A . Pediatric Bone Marrow Failure: A Broad Landscape in Need of Personalized Management. J Clin Med. 2023; 12(22). PMC: 10672506. DOI: 10.3390/jcm12227185. View

4.
Pickar-Oliver A, Gersbach C . The next generation of CRISPR-Cas technologies and applications. Nat Rev Mol Cell Biol. 2019; 20(8):490-507. PMC: 7079207. DOI: 10.1038/s41580-019-0131-5. View

5.
Vicente C, Conchillo A, Garcia-Sanchez M, Odero M . The role of the GATA2 transcription factor in normal and malignant hematopoiesis. Crit Rev Oncol Hematol. 2011; 82(1):1-17. DOI: 10.1016/j.critrevonc.2011.04.007. View