CRISPR/Cas9-mediated genome editing in human stem cell-derived cardiomyocytes: Applications for cardiovascular disease modelling and cardiotoxicity screening

Christidi, Effimia; Huang, Haojun; Brunham, Liam R.

doi:10.1016/j.ddtec.2018.06.002

Cited by 19 publications

(14 citation statements)

References 82 publications

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“…Human pluripotent stem cells (hPSCs) which encompass both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), is an attractive option for in vitro atherosclerosis model system [61]. Both cell lines can be reprogrammed and differentiated into specific cells for functional analysis.…”

Section: Types Of Cells Used In Crispr/cas9 Applicationsmentioning

confidence: 99%

Harnessing the Potential of CRISPR/Cas in Atherosclerosis: Disease Modeling and Therapeutic Applications

Siew

Tang

Kong

et al. 2021

IJMS

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Atherosclerosis represents one of the major causes of death globally. The high mortality rates and limitations of current therapeutic modalities have urged researchers to explore potential alternative therapies. The clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system is commonly deployed for investigating the genetic aspects of Atherosclerosis. Besides, advances in CRISPR/Cas system has led to extensive options for researchers to study the pathogenesis of this disease. The recent discovery of Cas9 variants, such as dCas9, Cas9n, and xCas9 have been established for various applications, including single base editing, regulation of gene expression, live-cell imaging, epigenetic modification, and genome landscaping. Meanwhile, other Cas proteins, such as Cas12 and Cas13, are gaining popularity for their applications in nucleic acid detection and single-base DNA/RNA modifications. To date, many studies have utilized the CRISPR/Cas9 system to generate disease models of atherosclerosis and identify potential molecular targets that are associated with atherosclerosis. These studies provided proof-of-concept evidence which have established the feasibility of implementing the CRISPR/Cas system in correcting disease-causing alleles. The CRISPR/Cas system holds great potential to be developed as a targeted treatment for patients who are suffering from atherosclerosis. This review highlights the advances in CRISPR/Cas systems and their applications in establishing pathogenetic and therapeutic role of specific genes in atherosclerosis.

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Section: Types Of Cells Used In Crispr/cas9 Applicationsmentioning

confidence: 99%

Harnessing the Potential of CRISPR/Cas in Atherosclerosis: Disease Modeling and Therapeutic Applications

Siew

Tang

Kong

et al. 2021

IJMS

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“…In another report, this editing tool has been used to eliminate inactivated genes in mature CMs through the Adeno-associated virus 9 (AAV9)- sgRNAs system [76]; it has also been used for editing the mitochondrial genome in order to control membrane potential disruption and cell growth inhibition, which are related to cancer genesis in transplanted tissues [40]. Moreover, the CRISPR/Cas9 system has been applied to human stem cell-derived CMs for cardiovascular disease modeling and cardiotoxicity screening; enabling studies of new cardiovascular disease treatments and drug-induced cardiotoxicity [77]. In addition, the CRISPR/Cas9 system can address safety concerns by reducing immunogenicity and even the risk of arrhythmia by removing the mutant ryanodine receptor 2 (RYP2) from the multimeric complexes [78].…”

Section: Genome Editing and Stem Cell Differentiationmentioning

confidence: 99%

Cardiac tissue engineering: state-of-the-art methods and outlook

et al. 2019

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The purpose of this review is to assess the state-of-the-art fabrication methods, advances in genome editing, and the use of machine learning to shape the prospective growth in cardiac tissue engineering. Those interdisciplinary emerging innovations would move forward basic research in this field and their clinical applications. The long-entrenched challenges in this field could be addressed by novel 3-dimensional (3D) scaffold substrates for cardiomyocyte (CM) growth and maturation. Stem cell-based therapy through genome editing techniques can repair gene mutation, control better maturation of CMs or even reveal its molecular clock. Finally, machine learning and precision control for improvements of the construct fabrication process and optimization in tissue-specific clonal selections with an outlook of cardiac tissue engineering are also presented.

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“…The CRISPR/Cas9 system provides scientists with a tool to create hiPSC isogenic controls by introducing targeted mutations in a cell line that can then be compared to the unmodified line. [153][154][155] This technique can be used to induce a phenotype via introduction of variants into control hiPSCs, especially if patient samples are difficult to obtain. Additionally, where samples from affected patients are available, variants can be corrected to determine if this results in phenotypic improvement in response to drug exposure.…”

Section: Genetic Manipulation Of Hipscsmentioning

confidence: 99%

hiPSCs in cardio-oncology: deciphering the genomics

Pinheiro

Fetterman

Burridge

2019

Cardiovascular Research

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The genomic predisposition to oncology-drug-induced cardiovascular toxicity has been postulated for many decades. Only recently has it become possible to experimentally validate this hypothesis via the use of patient-specific human-induced pluripotent stem cells (hiPSCs) and suitably powered genome-wide association studies (GWAS). Identifying the individual single nucleotide polymorphisms (SNPs) responsible for the susceptibility to toxicity from a specific drug is a daunting task as this precludes the use of one of the most powerful tools in genomics: comparing phenotypes to close relatives, as these are highly unlikely to have been treated with the same drug. Great strides have been made through the use of candidate gene association studies (CGAS) and increasingly large GWAS studies, as well as in vivo whole-organism studies to further our mechanistic understanding of this toxicity. The hiPSC model is a powerful technology to build on this work and identify and validate causal variants in mechanistic pathways through directed genomic editing such as CRISPR. The causative variants identified through these studies can then be implemented clinically to identify those likely to experience cardiovascular toxicity and guide treatment options. Additionally, targets identified through hiPSC studies can inform future drug development. Through careful phenotypic characterization, identification of genomic variants that contribute to gene function and expression, and genomic editing to verify mechanistic pathways, hiPSC technology is a critical tool for drug discovery and the realization of precision medicine in cardio-oncology.

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CRISPR/Cas9-mediated genome editing in human stem cell-derived cardiomyocytes: Applications for cardiovascular disease modelling and cardiotoxicity screening

Cited by 19 publications

References 82 publications

Harnessing the Potential of CRISPR/Cas in Atherosclerosis: Disease Modeling and Therapeutic Applications

Harnessing the Potential of CRISPR/Cas in Atherosclerosis: Disease Modeling and Therapeutic Applications

Cardiac tissue engineering: state-of-the-art methods and outlook

hiPSCs in cardio-oncology: deciphering the genomics

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