Editing the genome of hiPSC with CRISPR/Cas9: disease models

Bassett, Andrew

doi:10.1007/s00335-017-9684-9

Cited by 82 publications

(73 citation statements)

References 158 publications

(173 reference statements)

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“…properties that require examination at the single cell level in multiple cells from 98 a large number of cell lines. However, a more direct way to examine the effect 99 of a mutation independent of genetic background is to compare the cellular 100 changes caused by a single mutation in isogenic pairs of control and mutant 101 iPSC lines (Bassett, 2017 to generate an isogenic corrected line by removing the SCN1A mutation (Liu et 105 al., 2016). Comparison of the isogenic corrected versus the patient line 106 revealed a decrease in sodium current density in inhibitory neurons in the 107 patient line.…”

Section: Introduction 50mentioning

confidence: 99%

Comparisons of dual isogenic human iPSC pairs identify functional alterations directly caused by an epilepsy associatedSCN1Amutation

Xie¹,

Ng²,

Safrina³

et al. 2019

Preprint

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Over 1250 mutations in SCN1A, the Nav1.1 voltage-gated sodium channel gene, are associated with seizure disorders including GEFS+. To evaluate how a specific mutation, independent of genetic background, causes seizure activity we generated two pairs of isogenic human iPSC lines by CRISPR/Cas9 gene editing. One pair is a control line from an unaffected sibling, and the mutated control carrying the GEFS+ K1270T SCN1A mutation. The second pair is a GEFS+ patient line with the K1270T mutation, and the corrected patient line. By comparing the electrophysiological properties in inhibitory and excitatory iPSC-derived neurons from these pairs, we found the K1270T mutation causes cell type-specific alterations in sodium current density and evoked firing, resulting in hyperactive neural networks. We also identified differences associated with genetic background and interaction between the mutation and genetic background. Comparisons within and between dual pairs of isogenic iPSC-derived neuronal cultures provide a novel platform for evaluating cellular mechanisms underlying a disease phenotype and for developing patient-specific anti-seizure therapies.

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Section: Introduction 50mentioning

confidence: 99%

Comparisons of dual isogenic human iPSC pairs identify functional alterations directly caused by an epilepsy associatedSCN1Amutation

Xie¹,

Ng²,

Safrina³

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…The advent of human‐induced pluripotent stem cell (hiPSC) and targeted genome editing technologies have provided a unique opportunity to establish cellular models of disease, and to repair those genetic disorders in hiPSC from individual patients (Bassett, ). Specific mutations have been introduced into iPSCs and iPSC‐derived cells using Cas9 and HDR‐mediated genome editing for the study of genetic diseases (Hou et al, ; Park, Dwyer, Congiusta, Whelan, & Theodoropoulos, ; Rong, Zhu, Xu, & Fu, ; Yang et al, ).…”

Section: Crispr‐based Genome Editing In Biomedical Investigationmentioning

confidence: 99%

“…The advent of human-induced pluripotent stem cell (hiPSC) and targeted genome editing technologies have provided a unique HUANG ET AL. | 3885 opportunity to establish cellular models of disease, and to repair those genetic disorders in hiPSC from individual patients (Bassett, 2017).…”

Section: Repairing Genetic Disorders In Pluripotent Cellsmentioning

confidence: 99%

CRISPR editing in biological and biomedical investigation

Huang

Wang

Zhao

2017

Journal Cellular Physiology

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Recently, clustered regularly interspaced short palindromic repeats (CRISPR) based genomic editing technologies have armed researchers with powerful new tools to biological and biomedical investigations. To further improve and expand its functionality, natural, and engineered CRISPR associated nine proteins (Cas9s) have been investigated, various CRISPR delivery strategies have been tested and optimized, and multiple schemes have been developed to ensure precise mammalian genome editing. Benefiting from those in-depth understanding and further development of CRISPR, versatile CRISPR-based platforms for genome editing have been rapidly developed to advance investigations in biology and biomedicine. In biological research area, CRISPR has been widely adopted in both fundamental and applied research fields, such as accurate base editing, transcriptional regulation, and genome-wide screening. In biomedical research area, CRISPR has also shown its extensive applicability in the establishment of animal models for genetic disorders especially those large animals and non-human primates models, and gene therapy to combat virus infectious diseases, to correct monogenic disorders in vivo or in pluripotent cells. In this prospect article, after highlighting recent developments of CRISPR systems, we outline different applications and current limitations of CRISPR use in biological and biomedical investigation. Finally, we provide a perspective for future development and potential risks of this multifunctional technology.

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“…Human pluripotent stem cells (hPSCs) are also important for genome editing technology, since they can continue to divide to form identical cell clones [7,41,42]. They can also produce specialized types of cells through differentiation.…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 99%

“…Genome editing technology enables engineering of the variant allele associated with a specific disease in human cultured cells with a uniform genetic background [7,8]. Phenotypic comparison of such edited cells can then demonstrate how a variant of interest can affect the cellular events that are relevant to a specific pathological condition [9,10].…”

Section: Introductionmentioning

confidence: 99%

Updated summary of genome editing technology in human cultured cells linked to human genetics studies

2017

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Current deep-sequencing technology provides a mass of nucleotide variations associated with human genetic disorders to accelerate the identification of causative mutations. To understand the etiology of genetic disorders, reverse genetics in human cultured cells is a useful approach for modeling a disease in vitro. However, gene targeting in human cultured cells is difficult because of their low activity of homologous recombination. Engineered endonucleases enable enhancement of the local activation of DNA repair pathways at the human genome target site to rewrite the desired sequence, thereby efficiently generating disease-modeling cultured cell clones. These edited cells can be used to explore the molecular functions of a causative gene product to uncover the etiological mechanisms. The correction of mutations in patient cells using genome editing technology could contribute to the development of unique gene therapies. This technology can also be applied to screening causative mutations. Rare genetic disorders and non-exonic mutation-caused diseases remain frontier in the field of human genetics as it is difficult to validate whether the extracted nucleotide variants are mutation or polymorphism. When isogenic human cultured cells with a candidate variant reproduce the pathogenic phenotypes, it is confirmed that the variant is a causative mutation.

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Editing the genome of hiPSC with CRISPR/Cas9: disease models

Cited by 82 publications

References 158 publications

Comparisons of dual isogenic human iPSC pairs identify functional alterations directly caused by an epilepsy associatedSCN1Amutation

Comparisons of dual isogenic human iPSC pairs identify functional alterations directly caused by an epilepsy associatedSCN1Amutation

CRISPR editing in biological and biomedical investigation

Updated summary of genome editing technology in human cultured cells linked to human genetics studies

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