CRISPR/Cas9 Genome-Editing System in Human Stem Cells: Current Status and Future Prospects

Zhang, Zhao; Zhang, Yuelin; Gao, Fei; Han, Shuo; Cheah, Kathryn S. E.; Tse, Hung‐Fat; Lian, Qizhou

doi:10.1016/j.omtn.2017.09.009

Cited by 90 publications

(75 citation statements)

References 149 publications

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“…Our advanced, deep bioinformatic analysis overcame some limitations in capture and coverage of WES, leading to a high diagnostic yield rate. Uncovering molecular defects can help us understand the complex pathogenesis of LS, paving the way for development of curative treatment options and potential therapeutic strategies, including stem cell‐derived mitochondrial donation or CRISPR/Cas9 genome editing . In genetically unsolved cases, RNA sequencing of muscle biopsy or induced pluripotent stem cells might be needed.…”

Section: Discussionmentioning

confidence: 99%

Genetic heterogeneity in Leigh syndrome: Highlighting treatable and novel genetic causes

et al. 2020

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Leigh syndrome (LS), the most common childhood mitochondrial disorder, has characteristic clinical and neuroradiologic features. Mutations in more than 75 genes have been identified in both the mitochondrial and nuclear genome, implicating a high degree of genetic heterogeneity in LS. To profile these genetic signatures and understand the pathophysiology of LS, we recruited 64 patients from 62 families who were clinically diagnosed with LS at Seoul National University Children's Hospital. Mitochondrial genetic analysis followed by whole‐exome sequencing was performed on 61 patients. Pathogenic variants in mitochondrial DNA were identified in 18 families and nuclear DNA mutations in 22. The following 17 genes analyzed in 40 families were found to have genetic complexity: MTATP6, MTND1, MTND3, MTND5, MTND6, MTTK, NDUFS1, NDUFV1, NDUFAF6, SURF1, SLC19A3, ECHS1, PNPT1, IARS2, NARS2, VPS13D, and NAXE. Two treatable cases had biotin‐thiamine responsive basal ganglia disease, and another three were identified as having defects in the newly recognized genes (VPS13D or NAXE). Variants in the nuclear genes that encoded mitochondrial aminoacyl tRNA synthetases were present in 27.3% of cases. Our findings expand the genetic and clinical spectrum of LS, showing genetic heterogeneity and highlighting treatable cases and those with novel genetic causes.

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Section: Discussionmentioning

confidence: 99%

Genetic heterogeneity in Leigh syndrome: Highlighting treatable and novel genetic causes

et al. 2020

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“…Promoted by its advantages over other gene drive systems—such as transcription activator-like effector nucleases (TALENs) and zinc finger nucleases (ZFNs)—used in genome editing technology, and over other genetic techniques such as RNA interference (RNAi) [ 84 , 89 , 90 ], the recently-discovered CRISPR/Cas9 (clustered regularly-interspaced short palindromic repeats/CRISPR-associated protein 9) system has flowered, and is being widely used in current research trials and applications to modify genome sequences in diverse species spanning microbes, plants, animals, to even humans [ 89 , 90 , 91 , 92 , 93 ]. In parallel, the use of CRISPR/Cas9 to drive anti- Schistosoma effector genes into the genome of naturally susceptible snail strains is being envisioned, and has become an important subject in current discussions [ 17 , 75 , 94 , 95 ].…”

Section: Transgenic Snail Methods For Schistosomiasis Controlmentioning

confidence: 99%

Treading the Path towards Genetic Control of Snail Resistance to Schistosome Infection

Famakinde¹

2018

TropicalMed

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Schistosomiasis remains the most important tropical snail-borne trematodiasis that threatens many millions of human lives. In achieving schistosomiasis elimination targets, sustainable control of the snail vectors represents a logical approach. Nonetheless, the ineffectiveness of the present snail control interventions emphasizes the need to develop new complementary strategies to ensure more effective control outcomes. Accordingly, the use of genetic techniques aimed at driving resistance traits into natural vector populations has been put forward as a promising tool for integrated snail control. Leveraging the Biomphalaria-Schistosoma model system, studies unraveling the complexities of the vector biology and those exploring the molecular basis of snail resistance to schistosome infection have been expanding in various breadths, generating many significant discoveries, and raising the hope for future breakthroughs. This review provides a compendium of relevant findings, and without neglecting the current existing gaps and potential future challenges, discusses how a transgenic snail approach may be adapted and harnessed to control human schistosomiasis.

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“…Despite the rapid evolution of genome editing, the approach still has multiple technical challenges that prevent efficient genome editing in established iPSCs. 100 First, unwanted offtarget mutations may occur. Although recent whole-genome sequencing results show that off target editing by CRISPR/Cas9 is very low in human stem cells, [101][102][103] this problem has been further reduced through additional strategies such as designing sgRNAs with very high specificity scores, using a modified Cas9 nuclease with improved binding specificity to sgRNAs, testing sgRNAs with different lengths and PAM sequences, and the delivery of purified gRNA and Cas9 protein as a CAS9-ribonucleoprotein (RNP) complex.…”

Section: Generation and Gene Editing Of Ipscsmentioning

confidence: 99%

Modeling genetic epilepsies in a dish

Niu

Parent

2019

Developmental Dynamics

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Human pluripotent stem cells (hPSCs), including embryonic and induced pluripotent stem cells, provide a powerful platform for mechanistic studies of disorders of neurodevelopment and neural networks. hPSC models of autism, epilepsy, and other neurological disorders are also advancing the path toward designing and testing precision therapies. The field is evolving rapidly with the addition of genome-editing approaches, expanding protocols for the two-dimensional (2D) differentiation of different neuronal subtypes, and three-dimensional (3D) human brain organoid cultures. However, the application of these techniques to study complex neurological disorders, including the epilepsies, remains a challenge. Here, we review previous work using both 2D and 3D hPSC models of genetic epilepsies, as well as recent advances in the field. We also describe new strategies for applying these technologies to disease modeling of genetic epilepsies, and discuss current challenges and future directions. K E Y W O R D S brain organoid, epilepsy, genome editing, human pluripotent stem cells, neurological disorder, seizure disorder

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CRISPR/Cas9 Genome-Editing System in Human Stem Cells: Current Status and Future Prospects

Cited by 90 publications

References 149 publications

Genetic heterogeneity in Leigh syndrome: Highlighting treatable and novel genetic causes

Genetic heterogeneity in Leigh syndrome: Highlighting treatable and novel genetic causes

Treading the Path towards Genetic Control of Snail Resistance to Schistosome Infection

Modeling genetic epilepsies in a dish

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