Translational potential of base-editing tools for gene therapy of monogenic diseases

Reshetnikov, Vasiliy V.; Chirinskaite, Angelina V.; Sopova, Julia V.; Ivanov, Roman; Leonova, E. I.

doi:10.3389/fbioe.2022.942440

Cited by 7 publications

(6 citation statements)

References 129 publications

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“…Off-target effects, where CRISPR-Cas9 inadvertently edits genes other than the intended targets, can lead to unintended consequences and complicate the interpretation of experimental results. Furthermore, the site-specific editing efficiency, crucial for precise gene correction, is naturally low in many cell types, which limits the applications of corrective gene editing [ 6 , 45 , 53 ]. Furthermore, variability in iPSC lines, due to differences in the genetic background of the donor cells and the reprogramming process, can affect the consistency of disease models and therapeutic outcomes.…”

Section: Technical Challenges In Disease Modeling and Gene Therapymentioning

confidence: 99%

Induced Pluripotent Stem Cells and CRISPR-Cas9 Innovations for Treating Alpha-1 Antitrypsin Deficiency and Glycogen Storage Diseases

Walsh,

Jin

2024

Cells

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Human induced pluripotent stem cell (iPSC) and CRISPR-Cas9 gene-editing technologies have become powerful tools in disease modeling and treatment. By harnessing recent biotechnological advancements, this review aims to equip researchers and clinicians with a comprehensive and updated understanding of the evolving treatment landscape for metabolic and genetic disorders, highlighting how iPSCs provide a unique platform for detailed pathological modeling and pharmacological testing, driving forward precision medicine and drug discovery. Concurrently, CRISPR-Cas9 offers unprecedented precision in gene correction, presenting potential curative therapies that move beyond symptomatic treatment. Therefore, this review examines the transformative role of iPSC technology and CRISPR-Cas9 gene editing in addressing metabolic and genetic disorders such as alpha-1 antitrypsin deficiency (A1AD) and glycogen storage disease (GSD), which significantly impact liver and pulmonary health and pose substantial challenges in clinical management. In addition, this review discusses significant achievements alongside persistent challenges such as technical limitations, ethical concerns, and regulatory hurdles. Future directions, including innovations in gene-editing accuracy and therapeutic delivery systems, are emphasized for next-generation therapies that leverage the full potential of iPSC and CRISPR-Cas9 technologies.

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Section: Technical Challenges In Disease Modeling and Gene Therapymentioning

confidence: 99%

Induced Pluripotent Stem Cells and CRISPR-Cas9 Innovations for Treating Alpha-1 Antitrypsin Deficiency and Glycogen Storage Diseases

Walsh,

Jin

2024

Cells

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“…It is also characterized by high precision, with BEs that can discriminate between the target base and multiple bystander bases within a narrow active window ( Jeong et al, 2020 ). Recent improved versions of classicals BEs are described in the review by Reshetnikov et al (2022) .…”

Section: Gene Editing Toolsmentioning

confidence: 99%

Hematopoietic stem and progenitors cells gene editing: Beyond blood disorders

et al. 2023

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Lessons learned from decades-long practice in the transplantation of hematopoietic stem and progenitor cells (HSPCs) to treat severe inherited disorders or cancer, have set the stage for the current ex vivo gene therapies using autologous gene-modified hematopoietic stem and progenitor cells that have treated so far, hundreds of patients with monogenic disorders. With increased knowledge of hematopoietic stem and progenitor cell biology, improved modalities for patient conditioning and with the emergence of new gene editing technologies, a new era of hematopoietic stem and progenitor cell-based gene therapies is poised to emerge. Gene editing has the potential to restore physiological expression of a mutated gene, or to insert a functional gene in a precise locus with reduced off-target activity and toxicity. Advances in patient conditioning has reduced treatment toxicities and may improve the engraftment of gene-modified cells and specific progeny. Thanks to these improvements, new potential treatments of various blood- or immune disorders as well as other inherited diseases will continue to emerge. In the present review, the most recent advances in hematopoietic stem and progenitor cell gene editing will be reported, with a focus on how this approach could be a promising solution to treat non-blood-related inherited disorders and the mechanisms behind the therapeutic actions discussed.

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“…The rapid development of base editing tools is directly fused with the improvement in bioinformatic approaches that predict base editing outcomes. Once these shortcomings are eliminated, they can be used in personalized medicine [ 92 ]. For the schematic visualization of CRISPR/Cas9 targeted base editing, see Fig.…”

Section: Crispr/cas9 and Other Cas Molecule-based Technologies Are In...mentioning

confidence: 99%

Multi-faceted CRISPR/Cas technological innovation aspects in the framework of 3P medicine

et al. 2023

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Since 2009, the European Association for Predictive, Preventive and Personalised Medicine (EPMA, Brussels) promotes the paradigm change from reactive approach to predictive, preventive, and personalized medicine (PPPM/3PM) to protect individuals in sub-optimal health conditions from the health-to-disease transition, to increase life-quality of the affected patient cohorts improving, therefore, ethical standards and cost-efficacy of healthcare to great benefits of the society at large. The gene-editing technology utilizing CRISPR/Cas gene-editing approach has demonstrated its enormous value as a powerful tool in a broad spectrum of bio/medical research areas. Further, CRISPR/Cas gene-editing system is considered applicable to primary and secondary healthcare, in order to prevent disease spread and to treat clinically manifested disorders, involving diagnostics of SARS-Cov-2 infection and experimental treatment of COVID-19. Although the principle of the proposed gene editing is simple and elegant, there are a lot of technological challenges and ethical considerations to be solved prior to its broadly scaled clinical implementation. This article highlights technological innovation beyond the state of the art, exemplifies current achievements, discusses unsolved technological and ethical problems, and provides clinically relevant outlook in the framework of 3PM.

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Translational potential of base-editing tools for gene therapy of monogenic diseases

Cited by 7 publications

References 129 publications

Induced Pluripotent Stem Cells and CRISPR-Cas9 Innovations for Treating Alpha-1 Antitrypsin Deficiency and Glycogen Storage Diseases

Induced Pluripotent Stem Cells and CRISPR-Cas9 Innovations for Treating Alpha-1 Antitrypsin Deficiency and Glycogen Storage Diseases

Hematopoietic stem and progenitors cells gene editing: Beyond blood disorders

Multi-faceted CRISPR/Cas technological innovation aspects in the framework of 3P medicine

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