A5067038145- Hemoglobinopathies and Related Disorders
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Iron Metabolism and Disorders
- Prenatal Screening and Diagnostics
- Mosquito-borne diseases and control
- Mitochondrial Function and Pathology
- Bacterial Identification and Susceptibility Testing
- Clinical Laboratory Practices and Quality Control
- Parvovirus B19 Infection Studies
- Neurogenetic and Muscular Disorders Research
- DNA and Nucleic Acid Chemistry
- Genetic Neurodegenerative Diseases
- RNA and protein synthesis mechanisms
Institut des Maladies Génétiques Imagine
2021-2024
Inserm
2021-2023
Université Paris Cité
2021-2023
Hôpital Foch
2019
Abstract Sickle cell disease and β-thalassemia affect the production of adult β-hemoglobin chain. The clinical severity is lessened by mutations that cause fetal γ-globin expression in life (i.e., hereditary persistence hemoglobin). Mutations clustering ~200 nucleotides upstream HBG transcriptional start sites either reduce binding LRF repressor or recruit KLF1 activator. Here, we use base editing to generate a variety −200 region promoters, including potent combinations four eight...
β-Thalassemia (BT) is one of the most common genetic diseases worldwide and caused by mutations affecting β-globin production. The only curative treatment allogenic hematopoietic stem/progenitor cells (HSPCs) transplantation, an approach limited compatible donor availability immunological complications. Therefore, transplantation autologous, genetically-modified HSPCs attractive therapeutic option. However, current gene therapy strategies based on use lentiviral vectors are not equally...
Sickle cell disease (SCD) is due to a mutation in the β-globin gene causing production of toxic sickle hemoglobin (HbS; α2βS2). Transplantation autologous hematopoietic stem and progenitor cells (HSPCs) transduced with lentiviral vectors (LVs) expressing an anti-sickling (βAS) promising treatment; however, it only partially effective, patients still present elevated HbS levels. Here, we developed bifunctional LV βAS3-globin artificial microRNA (amiRNA) specifically downregulating βS-globin...
Sickle cell disease (SCD) is a genetic anemia caused by the production of an abnormal adult hemoglobin. The clinical severity lessened elevated fetal hemoglobin (HbF) in adulthood. A promising therapy transplantation autologous, hematopoietic stem/progenitor cells (HSPCs) treated with CRISPR/Cas9 to downregulate HbF repressor BCL11A via generation double strand breaks (DSBs) +58-kb erythroid-specific enhancer. Here, further enhance without increasing mutagenic load, we targeted both and...
Abstract Sickle cell disease (SCD) is due to a mutation in the β-globin ( HBB ) gene causing production of toxic sickle hemoglobin (HbS, 2 β S ). Transplantation autologous hematopoietic stem/progenitor cells (HSPCs) transduced with lentiviral vectors (LVs) expressing an anti-sickling (βAS) promising treatment; however, it only partially effective and patients still present elevated HbS levels. Here, we developed bifunctional LV βAS3-globin artificial microRNA (amiR) specifically...
The monitoring of quality indicators, combined with a detailed risk analysis, validates the process automated blood culture. Here we report methodology 5 years for indicators at Biology Department Foch Hospital: volume sampled, proportion contaminants, positive cultures in each instrument and drawer, epidemiological indicator false-positive signals. results obtained were outside expected target sampled acceptable other indicators. analysis these leads us to discuss evolution more...