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CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells
Open accessAbstract
The β-haemoglobinopathies, such as sickle cell disease and β-thalassaemia, are caused by mutations in the β-globin (HBB) gene and affect millions of people worldwide. Ex vivo gene correction in patient-derived haematopoietic stem cells followed by autologous transplantation could be used to cure β-haemoglobinopathies. Here we present a CRISPR/Cas9 gene-editing system that combines Cas9 ribonucleoproteins and adeno-associated viral vector delivery of a homologous donor to achieve homologous recombination at the HBB gene in haematopoietic stem cells. Notably, we devise an enrichment model to purify a population of haematopoietic stem and progenitor cells with more than 90% targeted integration. We also show efficient correction of the Glu6Val mutation responsible for sickle cell disease by using patient-derived stem and progenitor cells that, after differentiation into erythrocytes, express adult β-globin (HbA) messenger RNA, which confirms intact transcriptional regulation of edited HBB alleles. Collectively, these preclinical studies outline a CRISPR-based methodology for targeting haematopoietic stem cells by homologous recombination at the HBB locus to advance the development of next-generation therapies for β-haemoglobinopathies.
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“Accordingly, several reports have shown efficient Glu6Val correction in SCD-HSPCs, although correction efficiency can sometimes be linked with off-target INDELs in the same edited population15,16,45,46.”
From A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells (2018) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“RNP delivery results in an initially high level of the genome editing machinery followed by rapid decay, leading to a “fast on, fast off” strategy that results in highly efficient editing while minimizing OTEs13–19.”
From A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells (2018) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“AAV6 homologous donor DNA templates are an efficient way to deliver donor templates for sensitive primary immune cells, including HSPCs and T-Cells15,35–40.”
From A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells (2018) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Recent studies have shown that disease-causing genetic errors can be corrected using CRISPR/Cas9 in long-term engrafting HSPCs that are preserved in downstream effector lineages15,16,24,25.”
From A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells (2018) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Major progress in delivering to 44 and handling HPSCs has resulted in formidable efficiencies of mutation correction or mitigation 18,45-47 that are expected to be curative.”
From The promise and challenge of therapeutic genome editing (2020) · cites this paper as [45]
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In the citing paper
“Furthermore, CRISPR/Cas9 system holds tremendous promise for gene therapy [46–51]. It can correct causal mutations in the original genome and rescue the disease phenotypes of monogenic disorders permanently, which currently represents the most translatable field in CRISPR/Cas9-mediated disease therapy.”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [49]
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Cites
A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012) · Science · doi:10.1126/science.1225829 · Cited by 17,116
The new frontier of genome engineering with CRISPR-Cas9
Doudna, J. A., & Charpentier, E. (2014) · Science · doi:10.1126/science.1258096 · Cited by 7,062
Development and Applications of CRISPR-Cas9 for Genome Engineering
Hsu, P. D., Lander, E. S., & Zhang, F. (2014) · Cell · doi:10.1016/j.cell.2014.05.010 · Cited by 5,762
Easy quantitative assessment of genome editing by sequence trace decomposition
Brinkman, E. K., Chen, T., Amendola, M., & van Steensel, B. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku936 · Cited by 2,390
Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia
Cavazzana-Calvo, M., Payen, E., Negre, O., Wang, G., Hehir, K., Fusil, F., Down, J., Denaro, M., Brady, T., Westerman, K., et al. (2010) · Nature · doi:10.1038/nature09328 · Cited by 1,276
Gene therapy returns to centre stage
Naldini, L. (2015) · Nature · doi:10.1038/nature15818 · Cited by 1,184
HSV-TK Gene Transfer into Donor Lymphocytes for Control of Allogeneic Graft-Versus-Leukemia
Bonini, C., Ferrari, G., Verzeletti, S., Servida, P., Zappone, E., Ruggieri, L., Ponzoni, M., Rossini, S., Mavilio, F., Traversari, C., et al. (1997) · Science · doi:10.1126/science.276.5319.1719 · Cited by 1,158
Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells
Hendel, A., Bak, R. O., Clark, J. T., Kennedy, A. B., Ryan, D. E., Roy, S., Steinfeld, I., Lunstad, B. D., Kaiser, R. J., Wilkens, A. B., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3290 · Cited by 1,090
Self-citationIsolation of a candidate human hematopoietic stem-cell population.
Baum, C. M., Weissman, I. L., Tsukamoto, A. S., Buckle, A., & Péault, B. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.7.2804 · Cited by 1,084
Hematopoietic stem cell: self‐renewal versus differentiation
Seita, J., & Weissman, I. L. (2010) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.86 · Cited by 997
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Li, H., Yang, Y., Hong, W., Huang, M., Wu, M., & Zhao, X. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0089-y · Cited by 1,829
Kato, G. J., Piel, F. B., Reid, C. D., Gaston, M. H., Ohene-Frempong, K., Krishnamurti, L., Smith, W. R., Panepinto, J. A., Weatherall, D. J., Costa, F. F., et al. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.10 · Cited by 1,501
CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response
Haapaniemi, E., Botla, S., Persson, J., Schmierer, B., & Taipale, J. (2018) · Nature Medicine · doi:10.1038/s41591-018-0049-z · Cited by 1,264
The promise and challenge of therapeutic genome editing
Doudna, J. A. (2020) · Nature · doi:10.1038/s41586-020-1978-5 · Cited by 1,126
Identification of preexisting adaptive immunity to Cas9 proteins in humans
Charlesworth, C. T., Deshpande, P. S., Dever, D. P., Camarena, J., Lemgart, V. T., Cromer, M. K., Vakulskas, C. A., Collingwood, M. A., Zhang, L., Bode, N. M., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0326-x · Cited by 1,093
Self-citation
Metadata
- Authors
- Dever, D. P., Bak, R. O., Reinisch, A., Camarena, J., Washington, G., Nicolas, C. E., Pavel-Dinu, M., Saxena, N., Wilkens, A. B., Mantri, S., Uchida, N., Hendel, A., Narla, A., Majeti, R., Weinberg, K. I., & Porteus, M. H.
- Affiliations
- Stanford University (US)
- Institute for Stem Cell Biology and Regenerative Medicine (US)
- Stanford Medicine (US)
- Corresponding author
- Porteus, Matthew H.
- ORCID
- Venue
- Nature
- Published
- 2016-11-07
- Volume
- 539
- Issue
- 7629
- Pages
- 384-389
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5898607
- OpenAlex
- W2547418311
- Semantic Scholar
- 91eb4c33902b14df9b2974a4ce8dc6e3c3a02125
- Cited by
- 864
- References
- 50
- Citations by year
- 2026: 45 · 2025: 75 · 2024: 80 · 2023: 93 · 2022: 76 · 2021: 120 · 2020: 93 · 2019: 90 · 2018: 99 · 2017: 89 · 2016: 4
- FWCI
- 48.84
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (5r01ai120766-02, R01-AI120766)
- National Eye Institute (PN2EY018244)
- National Institute of General Medical Sciences (T32GM007266)
- National Institute of Allergy and Infectious Diseases (R01-AI120766, R01AI097320)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Keywords
- CRISPR/Cas9 genome editing, beta-globin gene, hematopoietic stem cells, sickle cell disease, beta-thalassemia, homologous recombination, adeno-associated virus vectors, Cas9 ribonucleoprotein, autologous transplantation, reporter genes
- MeSH terms
- Gene Editing, Dependovirus, Alleles, Anemia, Sickle Cell, Animals, Cell Differentiation, Cell Separation, Erythrocytes, Female, Flow Cytometry, Hematopoietic Stem Cells, Humans, Microspheres, Mutation, RNA, Messenger, Genetic Therapy, Mice, SCID, Mice, Inbred NOD, beta-Thalassemia, Genes, Reporter, Gene Targeting, Antigens, CD34, Cell Lineage, beta-Globins, Magnets, Homologous Recombination, CRISPR-Cas Systems, CRISPR-Associated Proteins
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