In vivo genome editing improves motor function and extends survival in a mouse model of ALS

Gaj, Thomas; Ojala, David S.; Ekman, Freja K.; Byrne, Leah C.; Limsirichai, Prajit; Schaffer, David V.

doi:10.1126/sciadv.aar3952

Cited by 146 publications

(126 citation statements)

References 86 publications

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“…Approximately 20% of familial cases of ALS carry autosomal dominant mutations in the superoxide dismutase 1 (SOD1) gene. The Schaffer group demonstrated that disruption of mutant SOD1 expression in the G93A-SOD1 mouse model of ALS via in vivo CRISPR/Cas9 genome editing using an AAV vector resulted in delayed disease onset, improved motor function, and reduced muscle atrophy (Gaj et al 2017).…”

Section: Mice and Ratsmentioning

confidence: 99%

Genome editing methods in animal models

Lee

Yoon

Kim

2020

Animal Cells and Systems

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Genetically engineered animal models that reproduce human diseases are very important for the pathological study of various conditions. The development of the clustered regularly interspaced short palindromic repeats (CRISPR) system has enabled a faster and cheaper production of animal models compared with traditional gene-targeting methods using embryonic stem cells. Genome editing tools based on the CRISPR-Cas9 system are a breakthrough technology that allows the precise introduction of mutations at the target DNA sequences. In particular, this accelerated the creation of animal models, and greatly contributed to the research that utilized them. In this review, we introduce various strategies based on the CRISPR-Cas9 system for building animal models of human diseases and describe various in vivo delivery methods of CRISPR-Cas9 that are applied to disease models for therapeutic purposes. In addition, we summarize the currently available animal models of human diseases that were generated using the CRISPR-Cas9 system and discuss future directions. ARTICLE HISTORY

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Section: Mice and Ratsmentioning

confidence: 99%

Genome editing methods in animal models

Lee

Yoon

Kim

2020

Animal Cells and Systems

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“…Recently developed nuclease‐based gene‐editing technologies have already breathed new life into somatic gene therapy. CRISPR/Cas9‐based gene editing, with its high efficiency, flexibility, and accuracy, can be applied to correct mutations or inactivate defective exons in animal models or human cells with pathologies such as Duchenne muscular dystrophy (DMD), amyotrophic lateral sclerosis and Huntington's disease . Recently, researchers succeeded in eliminating an entire chromosome in different cell types, including human induced pluripotent stem (iPS) cells with trisomy 21 .…”

Section: Gene Therapy With Somatic Cell Gene Editingmentioning

confidence: 99%

The CRIPSR/Cas gene‐editing system—an immature but useful toolkit for experimental and clinical medicine

Yang

Huang

2019

Anim Models and Exp Med

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A Chinese scientist, Jiankui He, and his creation of the world's first genetically altered baby made headlines recently. As a newly developed gene‐editing technique, the CRISPR /Cas system should not be applied to human beings for reproductive purposes until it has been extensively tested. However, numerous experimental research studies in human somatic, germline cells, and even in embryos, have been conducted, which have shown CRISPR /Cas to be a useful tool for human genome editing and a potential therapeutic method for future clinical use.

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“…4 Recently, the CRISPR-Cas9-mediated allele knock-out genome editing strategy, based on non-homologous end joining (NHEJ) has been successfully applied to correct gain-of-function mutations via AAV. 5, 6, 7, 8 One of the unique advantages of the genome editing approach is that it allows local treatment of the genome, such that the approach does not depend on the size of the target gene. However, genome editing for loss-of-function mutations in larger genes that require local replacement of the mutated sequence with a wildtype counterpart (mutation replacement) has not been successful in treatment of neuronal disorders primarily affecting neurons, due to its low editing efficiency.…”

Section: Introductionmentioning

confidence: 99%

Single AAV-mediated scarless genome editing in dysfunctional retinal neurons mediates robust visual restoration in mice

Nishiguchi

Fujita

Miya

et al. 2019

Preprint

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The most versatile treatment for inherited disorders is to precisely replace a mutated sequence with its wildtype counterpart, thereby “normalizing” the genome. We developed a single AAV platform that allows this in retinal neurons with combined CRISPR-Cas9 and micro-homology-mediated end-joining. In blind mice, the platform rescued ~10% of the retinal neurons, resulting in an incredible ~10,000-fold improvement in light sensitivity, equivalent to the restoration mediated by conventional gene augmentation therapy.

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In vivo genome editing improves motor function and extends survival in a mouse model of ALS

Abstract: CRISPR-Cas9–mediated genome editing can be used to treat ALS in an animal model of the disease.

Cited by 146 publications

References 86 publications

Genome editing methods in animal models

Genome editing methods in animal models

The CRIPSR/Cas gene‐editing system—an immature but useful toolkit for experimental and clinical medicine

Single AAV-mediated scarless genome editing in dysfunctional retinal neurons mediates robust visual restoration in mice

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