ArticleBlood2011
Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers.
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Who cites it
168 citing papers in PubMed, 296 citations in OpenAlex.
- Generation of neural cells from DM1 induced pluripotent stem cells as cellular model for the study of central nervous system neuropathogenesis.Cellular reprogramming · 2013Trial
- Gene Correction of Wiskott-Aldrich syndrome iPS Cells Rescues Proplatelet Defects and Improves Platelet Size.Thrombosis and haemostasis · 2025Article
- Genome editing strategies for targeted correction of β-globin mutation in sickle cell disease: From bench to bedside.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Advanced therapy to cure diabetes: mission impossible is now possible?Frontiers in cell and developmental biology · 2024Review
- CRISPR/Cas-based gene editing in therapeutic strategies for beta-thalassemia.Human genetics · 2023Review
- Trichostatin A for Efficient CRISPR-Cas9 Gene Editing of Human Pluripotent Stem Cells.The CRISPR journal · 2023Article
- Propensity of Patient-Derived iPSCs for Retinal Differentiation: Implications for Autologous Cell Replacement.Stem cells translational medicine · 2023Article
- Precision Editing as a Therapeutic Approach for β-Hemoglobinopathies.International journal of molecular sciences · 2023Review
- Stem Cell-Based Therapeutic Approaches in Genetic Diseases.Advances in experimental medicine and biology · 2023Article
- Filamin C in cardiomyopathy: from physiological roles to DNA variants.Heart failure reviews · 2022Review
- Induced Pluripotent Stem Cells (iPSCs) and Gene Therapy: A New Era for the Treatment of Neurological Diseases.International journal of molecular sciences · 2021Review
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- Review
- Clustered regularly interspaced short palindromic repeats as an advanced treatment for Parkinson's disease.Brain and behavior · 2021Review
- Review
- NRF2 mediates γ-globin gene regulation through epigenetic modifications in a β-YAC transgenic mouse model.Experimental biology and medicine (Maywood, N.J.) · 2020Article
- Induced Pluripotent Stem Cell Meets Severe Combined Immunodeficiency.Cell journal · 2020Review
- Biallelic correction of sickle cell disease-derived induced pluripotent stem cells (iPSCs) confirmed at the protein level through serum-free iPS-sac/erythroid differentiation.Stem cells translational medicine · 2020Article
- CRISPR System: A High-throughput Toolbox for Research and Treatment of Parkinson's Disease.Cellular and molecular neurobiology · 2020Review
- Modeling Psychiatric Disorder Biology with Stem Cells.Current psychiatry reports · 2020Review
108 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Human induced pluripotent stem cells (iPSCs) bearing monogenic mutations have great potential for modeling disease phenotypes, screening candidate drugs, and cell replacement therapy provided the underlying disease-causing mutation can be corrected. Here, we report a homologous recombination-based approach to precisely correct the sickle cell disease (SCD) mutation in patient-derived iPSCs with 2 mutated β-globin alleles (β(s)/β(s)). Using a gene-targeting plasmid containing a loxP-flanked drug-resistant gene cassette to assist selection of rare targeted clones and zinc finger nucleases engineered to specifically stimulate homologous recombination at the β(s) locus, we achieved precise conversion of 1 mutated β(s) to the wild-type β(A) in SCD iPSCs. However, the resulting co-integration of the selection gene cassette into the first intron suppressed the corrected allele transcription. After Cre recombinase-mediated excision of this loxP-flanked selection gene cassette, we obtained "secondary" gene-corrected β(s)/β(A) heterozygous iPSCs that express at 25% to 40% level of the wild-type transcript when differentiated into erythrocytes. These data demonstrate that single nucleotide substitution in the human genome is feasible using human iPSCs. This study also provides a new strategy for gene therapy of monogenic diseases using patient-specific iPSCs, even if the underlying disease-causing mutation is not expressed in iPSCs.
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Registered trials
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.