In vivo genome editing of mucopolysaccharidosis I mice using the CRISPR/Cas9 system

Schuh, Roselena Silvestri; Poletto, Édina; Pasqualim, Gabriela; Tavares, Ângela Maria Vicente; Meyer, Fabíola Shons; Gonzalez, Esteban Alberto; Matte, Úrsula da Silveira; Teixeira, Hélder Ferreira; Baldo, Guilherme

doi:10.1016/j.jconrel.2018.08.031

Cited by 58 publications

(55 citation statements)

References 53 publications

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“…Mice were treated with a single injection of liposome-complexed plasmids at 2-3 days of age. IDUA production was increased, compared to the untreated controls, with serum IDUA levels reaching 5-7% of wild-type mice for up to 6 months [84]. IDUA tissue levels were increased in all analyzed organs, except for the brain, followed by a similar pattern of reduction in the GAG levels.…”

Section: In Vivo Approachesmentioning

confidence: 77%

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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Section: In Vivo Approachesmentioning

confidence: 77%

Genome Editing for Mucopolysaccharidoses

Poletto

Baldo

Gomez‐Ospina

2020

IJMS

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“…Standard of care treatment includes HSCT, which can increase survival and peripheral symptoms, and may slow the development of mild, but not of severe, cognitive impairment. ERT with laronidase (Aldurazyme) (Clarke et al, 1997) + + AAV (Hartung et al, 1999(Hartung et al, , 2004Desmaris et al, 2004), BMT (Kuehn et al, 2015;Pievani et al, 2015), Crispr (Miki et al, 2019), ERT (Tong et al, 2017;Le et al, 2018;Ghosh et al, 2019), HSCT (Watson et al, 2014;Azario et al, 2017), LV (Di , NVGT (Aronovich et al, 2007(Aronovich et al, , 2009Osborn et al, 2008Osborn et al, , 2011, RV (Chung et al, 2007) Idua (−/−) (Ohmi et al, 2003) + + AAV (Watson et al, 2006;Janson et al, 2014;Ou et al, 2019), BMT (Nan et al, 2012;Wolf et al, 2012), Crispr (Schuh et al, 2018), ERT (Piller Puicher et al, 2012;Pasqualim et al, 2015;Lizzi Lagranha et al, 2017), LV (Wang et al, 2009;da Silva et al, 2012;Ou et al, 2016), NVGT (Camassola et al, 2005;Stilhano et al, 2015), RV (Zheng et al, 2003;Baldo et al, 2013), ZFN (Ou et al, 2019) Idua (…”

Section: Mps Type I (Omim [Online Mendelian Inheritancementioning

confidence: 99%

“…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%

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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“…Activity modification of a genetically defective protein by epigenetic manipulation HDACi 109/RG2833 increases FXN mRNA levels and frataxin protein, with concomitant changes in the epigenetic state of the gene, in the treatment of Friedreich's ataxia (OMIM:229300) [29]. Activity modification of a genetically defective protein by genome editing CRISPR-Cas9-mediated gene editing is a potential treatment for Hurler syndrome (OMIM:607014) as established in cell and animal based studies [30] [31]. Activity modification of a genetically defective protein by transcriptional or translational modification Vitamin D in treating hyperprolinemia (OMIM:239500) and recombinant human erythropoietin (rhuEPO) in treating Friedreich's ataxia (OMIM:229300) are examples of drugs that enhance the activity of PRODH and FXN respectively by transcriptional modulation of PRODH in hyperprolinemia and increasing frataxin expression in Friedrich's ataxia [32] [33].…”

Section: Symptomatic Therapeutic Proceduresmentioning

confidence: 99%

DDIEM: Drug Database for Inborn Errors of Metabolism

Abdelhakim

McMurray

Syed

et al. 2020

Preprint

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Background: Inborn errors of metabolism (IEM) represent a subclass of rare inherited diseases caused by a wide range of defects in metabolic enzymes or their regulation. Of over a thousand characterized IEMs, only about half are understood at the molecular level, and overall the development of treatment and management strategies has proved challenging. An overview of the changing landscape of therapeutic approaches is helpful in assessing strategic patterns in the approach to therapy, but the information is scattered throughout the literature and public data resources.Results: We gathered data on therapeutic strategies for 299 diseases into the Drug Database for Inborn Errors of Metabolism (DDIEM). Therapeutic approaches, including both successful and ineffective treatments, were manually classified by their mechanisms of action using a new ontology.Conclusions: We present a manually curated, ontologically formalized knowledgebase of drugs, therapeutic procedures, and mitigated phenotypes. DDIEM is freely available through a web interface and for download at http://ddiem.phenomebrowser.net.

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In vivo genome editing of mucopolysaccharidosis I mice using the CRISPR/Cas9 system

Cited by 58 publications

References 53 publications

Genome Editing for Mucopolysaccharidoses

Genome Editing for Mucopolysaccharidoses

Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases

DDIEM: Drug Database for Inborn Errors of Metabolism

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