| dc.rights.license | open | en_US |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | BOUTIN, Julian | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | ROSIER, Juliette | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | CAPPELLEN, David | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | PRAT, Florence | |
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| dc.contributor.author | TOUTAIN, Jerome | |
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| dc.contributor.author | PENNAMEN, Perrine | |
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| dc.contributor.author | BOURON, Julie | |
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| dc.contributor.author | ROORYCK-THAMBO, Caroline | |
| hal.structure.identifier | Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn] | |
| dc.contributor.author | MERLIO, Jean-Philippe | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | LAMRISSI, Isabelle | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | CULLOT, Gregoire | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | AMINTAS, Samuel | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | GUYONNET-DUPERAT, Veronique | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | GED, Cecile | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | BLOUIN, Jean Marc | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | RICHARD, Emmanuel | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | DABERNAT, Sandrine | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | MOREAU-GAUDRY, Francois | |
| hal.structure.identifier | Biothérapies des maladies génétiques et cancers | |
| dc.contributor.author | BEDEL, Aurelie | |
| dc.date.accessioned | 2021-10-26T08:04:05Z | |
| dc.date.available | 2021-10-26T08:04:05Z | |
| dc.date.issued | 2021-08-13 | |
| dc.identifier.issn | 2041-1723 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/112869 | |
| dc.description.abstractEn | CRISPR-Cas9 is a promising technology for gene therapy. However, the ON-target genotoxicity of CRISPR-Cas9 nuclease due to DNA double-strand breaks has received little attention and is probably underestimated. Here we report that genome editing targeting globin genes induces megabase-scale losses of heterozygosity (LOH) from the globin CRISPR-Cas9 cut-site to the telomere (5.2 Mb). In established lines, CRISPR-Cas9 nuclease induces frequent terminal chromosome 11p truncations and rare copy-neutral LOH. In primary hematopoietic progenitor/stem cells, we detect 1.1% of clones (7/648) with acquired megabase LOH induced by CRISPR-Cas9. In-depth analysis by SNP-array reveals the presence of copy-neutral LOH. This leads to 11p15.5 partial uniparental disomy, comprising two Chr11p15.5 imprinting centers (H19/IGF2:IG-DMR/IC1 and KCNQ1OT1:TSS-DMR/IC2) and impacting H19 and IGF2 expression. While this genotoxicity is a safety concern for CRISPR clinical trials, it is also an opportunity to model copy-neutral-LOH for genetic diseases and cancers. | |
| dc.description.sponsorship | Génotoxicité induite par CRISPR-CAS9 - ANR-21-CE18-0002 | en_US |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
| dc.title.en | CRISPR-Cas9 globin editing can induce megabase-scale copy-neutral losses of heterozygosity in hematopoietic cells | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1038/s41467-021-25190-6 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie | en_US |
| dc.identifier.pubmed | 34389729 | en_US |
| bordeaux.journal | Nature Communications | en_US |
| bordeaux.volume | 12 | en_US |
| bordeaux.hal.laboratories | Maladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211 | en_US |
| bordeaux.issue | 1 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.identifier.funderID | Association Française contre les Myopathies | en_US |
| hal.identifier | hal-03403276 | |
| hal.version | 1 | |
| hal.date.transferred | 2021-10-26T08:04:13Z | |
| hal.export | true | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature%20Communications&rft.date=2021-08-13&rft.volume=12&rft.issue=1&rft.eissn=2041-1723&rft.issn=2041-1723&rft.au=BOUTIN,%20Julian&ROSIER,%20Juliette&CAPPELLEN,%20David&PRAT,%20Florence&TOUTAIN,%20Jerome&rft.genre=article | |
