ArticleNature communications2022
Ultra-deep sequencing validates safety of CRISPR/Cas9 genome editing in human hematopoietic stem and progenitor cells.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Applications of synthetic biology in biomedicine.Molecular biomedicine · 2026Review
- Article
- Novel CRISPR-Cas9 BAP1 knockout pre-clinical tumor model recapitulates human melanoma tumorigenesis and immune evolution.Communications biology · 2026Article
- Peptide-enabled ribonucleoprotein delivery for CRISPR engineering (PERC) in primary human immune cells and hematopoietic stem cells.Nature protocols · 2025Review
- Hematopoietic stem cell gene therapy for the treatment of X-linked agammaglobulinemia.Molecular therapy. Methods & clinical development · 2025Article
- Genome Editing in Gynecological Oncology: The Emerging Role of CRISPR/Cas9 in Precision Cancer Therapy.Therapeutic innovation & regulatory science · 2025Review
- A CRISPR mis-insertion in the Zic3 5'UTR inhibits in vivo translation and is predicted to result in formation of an mRNA stem-loop hairpin.Biology open · 2025Article
- DNA-PKcs inhibition improves sequential gene insertion of the full-lengthMolecular therapy. Nucleic acids · 2024Article
- Enhancement of erythropoietic output by Cas9-mediated insertion of a natural variant in haematopoietic stem and progenitor cells.Nature biomedical engineering · 2024Article
- Quantifying allele-specific CRISPR editing activity with CRISPECTOR2.0.Nucleic acids research · 2024Article
- DNA-PKcs Inhibition Improves Sequential Gene Insertion of the Full-LengthbioRxiv : the preprint server for biology · 2024Article
- Regulatory Assessment of Casgevy for the Treatment of Transfusion-Dependent β-Thalassemia and Sickle Cell Disease with Recurrent Vaso-Occlusive Crises.Current issues in molecular biology · 2024Review
- A simultaneous knockout knockin genome editing strategy in HSPCs potently inhibits CCR5- and CXCR4-tropic HIV-1 infection.Cell stem cell · 2024Article
- Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy.Molecular cancer · 2024Review
- Epitope-engineered human hematopoietic stem cells are shielded from CD123-targeted immunotherapy.The Journal of experimental medicine · 2023Article
- RNA polymerase II pausing temporally coordinates cell cycle progression and erythroid differentiation.Developmental cell · 2023Article
- The p53 challenge of hematopoietic stem cell gene editing.Molecular therapy. Methods & clinical development · 2023Review
- Genome Editing in Engineered T Cells for Cancer Immunotherapy.Human gene therapy · 2023Review
- Whole genomic analysis reveals atypical non-homologous off-target large structural variants induced by CRISPR-Cas9-mediated genome editing.Nature communications · 2023Article
- Efficient correction ofMolecular therapy. Nucleic acids · 2023Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As CRISPR-based therapies enter the clinic, evaluation of safety remains a critical and active area of study. Here, we employ a clinical next generation sequencing (NGS) workflow to achieve high sequencing depth and detect ultra-low frequency variants across exons of genes associated with cancer, all exons, and genome wide. In three separate primary human hematopoietic stem and progenitor cell (HSPC) donors assessed in technical triplicates, we electroporated high-fidelity Cas9 protein targeted to three loci (AAVS1, HBB, and ZFPM2) and harvested genomic DNA at days 4 and 10. Our results demonstrate that clinically relevant delivery of high-fidelity Cas9 to primary HSPCs and ex vivo culture up to 10 days does not introduce or enrich for tumorigenic variants and that even a single SNP in a gRNA spacer sequence is sufficient to eliminate Cas9 off-target activity in primary, repair-competent human HSPCs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.