Zinc-finger nuclease-mediated correction of α-thalassemia in iPS cells

Chang, Chan Jung; Bouhassira, Eric E.

doi:10.1182/blood-2012-03-420703

Cited by 83 publications

(51 citation statements)

References 34 publications

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“…Recently, ZFN-mediated disruption of the TAP2 gene in hiPSCs made it possible to produce an unlimited amount of antigen-presenting cells for vaccination therapy (14). ZFN-mediated insertion of transgenes into the genomic safe harbor locus (AAVS1) of hiPSCs has been used to engineer cells for in vivo imaging and to correct the globin imbalance in ␣-thalassemia (15,16). In the case of HDR, ZFNs greatly simplify the experimental design, as short oligonucleotides may be used as templates, and antibiotic selection may be omitted (17).…”

Section: Genome Editing With Synthetic Nucleasesmentioning

confidence: 99%

A Cut above the Rest: Targeted Genome Editing Technologies in Human Pluripotent Stem Cells

Suzuki

Kim

et al. 2014

Journal of Biological Chemistry

114

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Human pluripotent stem cells (hPSCs) offer unprecedented opportunities to study cellular differentiation and model human diseases. The ability to precisely modify any genomic sequence holds the key to realizing the full potential of hPSCs. Thanks to the rapid development of novel genome editing technologies driven by the enormous interest in the hPSC field, genome editing in hPSCs has evolved from being a daunting task a few years ago to a routine procedure in most laboratories. Here, we provide an overview of the mainstream genome editing tools, including zinc finger nucleases, transcription activator-like effector nucleases, clustered regularly interspaced short palindromic repeat/CAS9 RNA-guided nucleases, and helper-dependent adenoviral vectors. We discuss the features and limitations of these technologies, as well as how these factors influence the utility of these tools in basic research and therapies.The discovery of induced pluripotent stem cells (iPSCs) 5 seven years ago has reignited the enthusiasm for cell-based therapy. The ability of iPSCs to undergo unlimited division while maintaining genomic integrity provides a way to overcome the senescence barrier of aged somatic cells. The capacity of iPSCs to differentiate into cells of the three germ layers has been extensively documented in the field. Taken together, it is not hard to appreciate why human iPSC (hiPSC)-based autologous transplantation is heralded as the future of regenerative medicine (Fig. 1). One area that has drawn great interest is correction of genetic diseases in patient-specific hiPSCs with a prospect of personalized cell therapy.Pluripotent stem cells are especially amenable for genome editing because they can undergo extensive tissue culture manipulations, such as drug selection and clonal expansion, while still maintaining their pluripotency and genome stability. Gene targeting in mouse embryonic stem cells by homologous recombination (HR) has proven to be a staple technique for studying gene function (1, 2). However, the same strategy does not translate well into human embryonic stem cells (hESCs) or hiPSCs (3). Although the classical HR method has been successfully used to generate knock-in reporter lines and to correct gene mutations in hESCs, the reported targeting efficiencies are at least several orders of magnitude lower than what is achievable in mouse embryonic stem cells (4,5). This is likely due to the intrinsic differences in the DNA repair process between humans and mice, as measures to improve single-cell survival and DNA transfection did not have a dramatic effect on gene targeting efficiency (6, 7). However, other methods aimed at promoting HR proved more fruitful (3). In the past several years, there has been a spike of interest in genome editing in hESCs and hiPSCs, possibly due to the potential of this technology in modeling and correcting a myriad of genetic diseases (8,9). This has fueled a rapid development in novel technologies for targeted modification of the human genome. Here, we aim to provide a timely u...

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Section: Genome Editing With Synthetic Nucleasesmentioning

confidence: 99%

A Cut above the Rest: Targeted Genome Editing Technologies in Human Pluripotent Stem Cells

Suzuki

Kim

et al. 2014

Journal of Biological Chemistry

114

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“…102 The mutation that results in synthesis of a sickle b-globin has been corrected in human induced pluripotent stem (iPS) cells providing proof of principal that this is a potentially viable approach. [103][104][105] The nuclease methodology has also been used to achieve correction of a-thalassemia in iPS cells 106 as well as genetic correction of b-thalassemia mutations in such cells. 107 Another potential application is the creation of genomic safe harbors that facilitate high b-globin transgene expression.…”

Section: Nuclease-mediated Correction Of Blood Disordersmentioning

confidence: 99%

Development of gene therapy for blood disorders: an update

Nienhuis

2013

Blood

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This review addresses the current status of gene therapy for immunodeficiencies, chronic granulomatous disease, suicide gene therapy for graft-versus-host disease, viral infections, malignant hematologic disorders, hemophilia, and the hemoglobin disorders. New developments in vector design have fostered improved expression as well as enhanced safety, particularly of integrating retroviral vectors. Several immunodeficiencies have been treated successfully by stem cell–targeted, retroviral-mediated gene transfer with reconstitution of the immune system following infusion of the transduced cells. In a trial for hemophilia B, long-term expression of human FIX has been observed following adeno-associated viral vector–mediated gene transfer into the liver. This approach should be successful in treating any disorder in which liver production of a specific protein is therapeutic.

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“…Therefore, pluripotent stem cells such as ESCs and iPSCs are able to create RBCs with universal O and rhesus (RhD)-negative blood types. The use of iPSC technology could also be applied to modify the mutated genes from patients with inherited RBC disorders, such as sickle cell anemia [17] and α-thalassemia [18]. Several groups have generated gene-corrected β-thalassemia iPSCs from patients; these could be induced to differentiate into hematopoietic progenitor cells and then into erythroblasts expressing normal β-globin [1921].…”

Section: Pluripotent Stem Cell-derived Hscs and Rbcsmentioning

confidence: 99%

From stem cells to red blood cells: how far away from the clinical application?

Xie

Pei

2014

Sci. China Life Sci.

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The generation of red blood cells (RBCs) from stem cells provides a solution for deficiencies in blood transfusion. Currently, primary hematopoietic stem cells, embryonic stem cells and induced pluripotent stem cells have shown the potential to produce fully mature RBCs. Here, we discuss the advantages, induction protocols, progress and possible clinical applications of stem cells in RBC production. stem cells, red blood cells, differentiation, clinical application Citation:Xie XY, Li YH, Pei XT. From stem cells to red blood cells: how far away from the clinical application?.

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Zinc-finger nuclease-mediated correction of α-thalassemia in iPS cells

Cited by 83 publications

References 34 publications

A Cut above the Rest: Targeted Genome Editing Technologies in Human Pluripotent Stem Cells

A Cut above the Rest: Targeted Genome Editing Technologies in Human Pluripotent Stem Cells

Development of gene therapy for blood disorders: an update

From stem cells to red blood cells: how far away from the clinical application?

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