Generation of a heterozygous COL1A1 (c.3969_3970insT) osteogenesis imperfecta mutation human iPSC line, MCRIi001-A-1, using CRISPR/Cas9 editing

Far, Hani Hosseini; Patria, Yudha Nur; Motazedian, Ali; Elefanty, Andrew G.; Lamandé, Shireen R.; Bateman, John F.

doi:10.1016/j.scr.2019.101449

Cited by 13 publications

(6 citation statements)

References 5 publications

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“…Currently, CRISPR-Cas9 is the most popular and widely adopted geneediting technology in the field of genetic disorders, despite its clinical applications are still limited. 238 The development of COL1A1 mutant iPSCs, a crucial cell line facilitating research into the causes and treatments of OI disorders, was achieved through the application of CRISPR-Cas9 tools by Hosseini Far et al 239 In a parallel study, McGowan et al harnessed the power of CRISPR-Cas9 genome editing to enhance osteoblast development and promote bone healing in a zebrafish model. Their approach involved the modification of the Wnt16 gene, leading to increased efficacy in stimulating osteoblast development and improving bone healing when the edited gene was introduced at the zebrafish egg stage.…”

Section: ■ Current and Future Therapy In Oimentioning

confidence: 99%

Emerging Landscape of Osteogenesis Imperfecta Pathogenesis and Therapeutic Approaches

Sun,

Li,

Wang

et al. 2024

ACS Pharmacol. Transl. Sci.

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Osteogenesis imperfecta (OI) is an uncommon genetic disorder characterized by shortness of stature, hearing loss, poor bone mass, recurrent fractures, and skeletal abnormalities. Pathogenic variations have been found in over 20 distinct genes that are involved in the pathophysiology of OI, contributing to the disorder's clinical and genetic variability. Although medications, surgical procedures, and other interventions can partially alleviate certain symptoms, there is still no known cure for OI. In this Review, we provide a comprehensive overview of genetic pathogenesis, existing treatment modalities, and new developments in biotechnologies such as gene editing, stem cell reprogramming, functional differentiation, and transplantation for potential future OI therapy.

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Section: ■ Current and Future Therapy In Oimentioning

confidence: 99%

Emerging Landscape of Osteogenesis Imperfecta Pathogenesis and Therapeutic Approaches

Sun,

Li,

Wang

et al. 2024

ACS Pharmacol. Transl. Sci.

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“…Proof-of-principle for such functional testing has been described using CRISPR/Cas9 gene editing to engineer COL1A1 OI patient mutations into induced pluripotent stem cells. (34,35) While these cell lines represent valuable resources to study the mechanisms of specific mutations, such approaches remain expensive and poorly amenable for diagnostic testing of individual novel VUS.…”

Section: Identifying Gene Variants Associated With Bone Fragilitymentioning

confidence: 99%

“…(111) Base-editing still requires delivery with dual-AAV vectors; however, a recent study highlighted a new base-editing enzyme featuring a cleavable deoxycytidine deaminase inhibitor domain that reduces off-target mutations. (112) • Proof-of-principle for in vitro assessment of OI mutations (34,35) • Affordable and broadly accessible mutation testing for OI patients Targeting of AAV vectors to the skeleton…”

Section: Gene Addition Therapymentioning

confidence: 99%

Curative Cell and Gene Therapy for Osteogenesis Imperfecta

Lee

O’Donohue

Ginn

et al. 2020

Journal of Bone and Mineral Research

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Osteogenesis imperfecta (OI) describes a series of genetic bone fragility disorders that can have a substantive impact on patient quality of life. The multidisciplinary approach to management of children and adults with OI primarily involves the administration of antiresorptive medication, allied health (physiotherapy and occupational therapy), and orthopedic surgery. However, advances in gene editing technology and gene therapy vectors bring with them the promise of gene-targeted interventions to provide an enduring or perhaps permanent cure for OI. This review describes emergent technologies for cell-and gene-targeted therapies, major hurdles to their implementation, and the prospects of their future success with a focus on bone disorders.

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“…In patients with a confirmed genetic diagnosis, gene editing could be used correct the mutation in their specific hiPSC line (Yanai et al, 2019); for instance, CRISPR/Cas9 editing of a deep intronic mutation in CEP290 removed the cryptic splice site and restored CEP290 expression (Burnight et al, 2018). Gene editing can also be used to introduce a known mutation into wild type hiPSCs where patient cells are not available as demonstrated by the generation of an hiPSC line with a single base insertion in the COL1A1 gene (c.3969_3970insT) found in patients with osteogenesis imperfecta (Hosseini Far et al, 2019). Introducing a known mutation into wild type hiPSCs can also be used as a control in disease models to ascertain its causative nature e.g., assessing the pathogenicity of induced MYL3 variants associated with hypertrophic cardiomyopathy (Ma et al, 2018b).…”

Section: Human Induced Pluripotent Stem Cellsmentioning

confidence: 99%

The Use of Induced Pluripotent Stem Cells as a Model for Developmental Eye Disorders

Eintracht¹,

Toms

Moosajee

2020

Front. Cell. Neurosci.

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Approximately one-third of childhood blindness is attributed to developmental eye disorders, of which 80% have a genetic cause. Eye morphogenesis is tightly regulated by a highly conserved network of transcription factors when disrupted by genetic mutations can result in severe ocular malformation. Human-induced pluripotent stem cells (hiPSCs) are an attractive tool to study early eye development as they are more physiologically relevant than animal models, can be patient-specific and their use does not elicit the ethical concerns associated with human embryonic stem cells. The generation of self-organizing hiPSC-derived optic cups is a major advancement to understanding mechanisms of ocular development and disease. Their development in vitro has been found to mirror that of the human eye and these early organoids have been used to effectively model microphthalmia caused by a VSX2 variant. hiPSC-derived optic cups, retina, and cornea organoids are powerful tools for future modeling of disease phenotypes and will enable a greater understanding of the pathophysiology of many other developmental eye disorders. These models will also provide an effective platform for identifying molecular therapeutic targets and for future clinical applications.

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Generation of a heterozygous COL1A1 (c.3969_3970insT) osteogenesis imperfecta mutation human iPSC line, MCRIi001-A-1, using CRISPR/Cas9 editing

Cited by 13 publications

References 5 publications

Emerging Landscape of Osteogenesis Imperfecta Pathogenesis and Therapeutic Approaches

Emerging Landscape of Osteogenesis Imperfecta Pathogenesis and Therapeutic Approaches

Curative Cell and Gene Therapy for Osteogenesis Imperfecta

The Use of Induced Pluripotent Stem Cells as a Model for Developmental Eye Disorders

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