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Gene Editing Correc...
Gene Editing Corrects In Vitro a G > A GLB1 Transition from a GM1 Gangliosidosis Patient
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Leclerc, D. (author)
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Goujon, L. (author)
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Jaillard, S. (author)
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Nouyou, B. (author)
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Cluzeau, L. (author)
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Damaj, L. (author)
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Dubourg, C. (author)
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Etcheverry, A. (author)
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Levade, T. (author)
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Froissart, R. (author)
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Dreano, S. (author)
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Guillory, X. (author)
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- Eriksson, Leif A, 1964 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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Launay, E. (author)
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Mouriaux, F. (author)
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Belaud-Rotureau, M. A. (author)
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Odent, S. (author)
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Gilot, D. (author)
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(creator_code:org_t)
- Mary Ann Liebert Inc, 2023
- 2023
- English.
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In: Crispr Journal. - : Mary Ann Liebert Inc. - 2573-1599 .- 2573-1602. ; 6:1
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Ganglioside-monosialic acid (GM1) gangliosidosis, a rare autosomal recessive disorder, is frequently caused by deleterious single nucleotide variants (SNVs) in GLB1 gene. These variants result in reduced beta-galactosidase (beta-gal) activity, leading to neurodegeneration associated with premature death. Currently, no effective therapy for GM1 gangliosidosis is available. Three ongoing clinical trials aim to deliver a functional copy of the GLB1 gene to stop disease progression. In this study, we show that 41% of GLB1 pathogenic SNVs can be replaced by adenine base editors (ABEs). Our results demonstrate that ABE efficiently corrects the pathogenic allele in patient-derived fibroblasts, restoring therapeutic levels of beta-gal activity. Off-target DNA analysis did not detect off-target editing activity in treated patient's cells, except a bystander edit without consequences on beta-gal activity based on 3D structure bioinformatics predictions. Altogether, our results suggest that gene editing might be an alternative strategy to cure GM1 gangliosidosis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- crispr-cas9 nucleases
- skeletal-muscle
- genomic DNA
- base
- deficiency
- expression
- cytosine
- brain
- mice
- Genetics & Heredity
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Leclerc, D.
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Goujon, L.
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Jaillard, S.
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Nouyou, B.
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Cluzeau, L.
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Damaj, L.
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show more...
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Dubourg, C.
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Etcheverry, A.
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Levade, T.
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Froissart, R.
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Dreano, S.
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Guillory, X.
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Eriksson, Leif A ...
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Launay, E.
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Mouriaux, F.
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Belaud-Rotureau, ...
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Odent, S.
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Gilot, D.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Crispr Journal
- By the university
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University of Gothenburg