Cas9-mediated allelic exchange repairs compound heterozygous recessive mutations in mice

Wang, Dan; Li, Jia; Song, Chun‐Qing; Tran, Karen; Mou, Haiwei; Wu, Pei Hsuan; Tai, Phillip W. L.; Mendonca, Craig A; Ren, Lingzhi; Wang, Blake Y.; Su, Qin; Gessler, Dominic J.; Zamore, Phillip D.; Xue, Wen; Gao, Guangping

doi:10.1038/nbt.4219

Cited by 39 publications

(25 citation statements)

References 32 publications

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“…We and others recently reported that CRISPR can correct this Fah mutation through HDR [16][17][18] or allelic exchange 19 . Following correction by CRISPR, liver cells expressing the Fah enzyme, through their selective advantage, expand and repopulate the liver 14 .…”

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confidence: 94%

Adenine base editing in an adult mouse model of tyrosinaemia

et al. 2019

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Unlike traditional CRISPR-Cas9 homology-directed repair, base editing can correct point mutations without supplying a DNA-repair template. Here, we show in a mouse model of tyrosinemia that hydrodynamic tail-vein injection of plasmid DNA encoding the adenine base editor (ABE) and a single guide RNA can correct an A>G splice-site mutation. ABE treatment partially restored splicing, generated fumarylacetoacetate hydrolase (Fah)-positive hepatocytes in the liver, and rescued weight loss in the animals. We also generated Fah+ hepatocytes in the liver via lipid-nanoparticle-mediated delivery of chemically modified sgRNA and an mRNA of a codon-optimized base editor that displayed higher base-editing efficiency than the standard ABE. Our findings suggest that adenosine base editing can be used for the correction of genetic disease in adult animals.

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confidence: 94%

Adenine base editing in an adult mouse model of tyrosinaemia

et al. 2019

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“…Organs traditionally known to be hard to correct, such as the heart valves and the brain, showed no improvement after therapy [85]. An additional study used CRISPR-Cas9 in vivo to target the common p.Trp402Ter mutation in a compound heterozygous mouse model of MPSI [86]. The strategy was shown to be partly efficacious in post-mitotic tissues like the heart.…”

Section: In Vivo Approachesmentioning

confidence: 99%

Genome Editing for Mucopolysaccharidoses

Poletto

Baldo

Gomez‐Ospina

2020

IJMS

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Genome editing holds the promise of one-off and potentially curative therapies for many patients with genetic diseases. This is especially true for patients affected by mucopolysaccharidoses as the disease pathophysiology is amenable to correction using multiple approaches. Ex vivo and in vivo genome editing platforms have been tested primarily on MSPI and MPSII, with in vivo approaches having reached clinical testing in both diseases. Though we still await proof of efficacy in humans, the therapeutic tools established for these two diseases should pave the way for other mucopolysaccharidoses. Herein, we review the current preclinical and clinical development studies, using genome editing as a therapeutic approach for these diseases. The development of new genome editing platforms and the variety of genetic modifications possible with each tool provide potential applications of genome editing for mucopolysaccharidoses, which vastly exceed the potential of current approaches. We expect that in a not-so-distant future, more genome editing-based strategies will be established, and individual diseases will be treated through multiple approaches.

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“…Furthermore, efforts to directly edit the genome and correct mutations are currently underway. Several groups have undertaken attempts using genome editing tools such as the CRISPR/Cas9 and ZFN systems to directly modify the endogenous Idua locus or introduce an exogenous Idua gene (Schuh et al, 2018;Wang et al, 2018;Gomez-Ospina et al, 2019). These techniques have shown preliminarily success at promoting functional IDUA and reducing GAG storage.…”

Section: Glycogen Storage Diseasementioning

confidence: 99%

“…W392X )(Wang et al, 2012) + + Crispr(Wang et al, 2018), ERT(Baldo et al, 2012) NST(Wang et al, 2012;Keeling et al, 2013) Idua (−/−)(Mendez et al, 2015) + + BT(Azario et al, 2017), HSCT(Gomez-Ospina et al, 2019) …”

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confidence: 99%

Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases

Favret

Weinstock

Feltri

et al. 2020

Front. Mol. Biosci.

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There are over 50 lysosomal hydrolase deficiencies, many of which cause neurodegeneration, cognitive decline and death. In recent years, a number of broad innovative therapies have been proposed and investigated for lysosomal storage diseases (LSDs), such as enzyme replacement, substrate reduction, pharmacologic chaperones, stem cell transplantation, and various forms of gene therapy. Murine models that accurately reflect the phenotypes observed in human LSDs are critical for the development, assessment and implementation of novel translational therapies. The goal of this review is to summarize the neurodegenerative murine LSD models available that recapitulate human disease, and the pre-clinical studies previously conducted. We also describe some limitations and difficulties in working with mouse models of neurodegenerative LSDs.

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Cas9-mediated allelic exchange repairs compound heterozygous recessive mutations in mice

Cited by 39 publications

References 32 publications

Adenine base editing in an adult mouse model of tyrosinaemia

Adenine base editing in an adult mouse model of tyrosinaemia

Genome Editing for Mucopolysaccharidoses

Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases

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