A5060062016- Economic Theory and Policy
- Economic theories and models
- Economic Growth and Productivity
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- European Union Policy and Governance
- Economic Theory and Institutions
- European Politics and Security
- Eastern European Communism and Reforms
- Hemoglobinopathies and Related Disorders
- RNA Interference and Gene Delivery
- Regional Development and Policy
- CAR-T cell therapy research
- Political Economy and Marxism
- Iron Metabolism and Disorders
- Social Sciences and Governance
- Business Strategy and Innovation
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Firm Innovation and Growth
- MicroRNA in disease regulation
- Lysosomal Storage Disorders Research
- Economic Development and Digital Transformation
- French Urban and Social Studies
- Immune Cell Function and Interaction
Genethon (France)
2016-2025
Inserm
2018-2025
Université Paris-Saclay
2020-2025
University of Foggia
2023-2025
The San Raffaele Telethon Institute for Gene Therapy
2004-2023
Université d'Évry Val-d'Essonne
2023
Sapienza University of Rome
2008-2020
Oncode Institute
2013-2017
The Netherlands Cancer Institute
2013-2017
University of Florence
2017
The efficacy and the mutation spectrum of genome editing methods can vary substantially depending on targeted sequence. A simple, quick assay to accurately characterize quantify induced mutations is therefore needed. Here we present TIDE, a method for this purpose that requires only pair PCR reactions two standard capillary sequencing runs. sequence traces are then analyzed by specially developed decomposition algorithm identifies major in projected site determines their frequency cell...
The spatial organization of chromosomes influences many nuclear processes including gene expression. cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased and duration with which embraces DNA determines degree to loops are enlarged. Cohesin's release factor WAPL restricts this extension also prevents between incorrectly oriented sites. reveal SCC2/SCC4 promotes formation topologically associated domains...
Therapies based on enhancing the numbers and/or function of T regulatory cells (Tregs) represent one most promising approaches to restoring tolerance in many immune-mediated diseases. Several groups have investigated whether human Tregs suitable for cellular therapy can be obtained by vitro expansion, conversion conventional into Tregs, or gene transfer FOXP3 transcription factor. To date, however, none these has resulted a homogeneous and stable population that is as potently suppressive ex...
Hematopoietic stem cell–specific microRNAs allow regulation of therapeutic transgene expression and enable effective gene therapy globoid cell leukodystrophy.
Editing the β-globin locus in hematopoietic stem cells is an alternative therapeutic approach for gene therapy of β-thalassemia and sickle cell disease. Using CRISPR/Cas9 system, we genetically modified human progenitor (HSPCs) to mimic large rearrangements associated with hereditary persistence fetal hemoglobin (HPFH), a condition that mitigates clinical phenotype patients β-hemoglobinopathies. We optimized compared efficiency plasmid-, lentiviral vector (LV)-, RNA-, ribonucleoprotein...
Editing the fetal γ-globin promoters in hematopoietic stem cells from sickle cell disease patients induces therapeutic levels.
Abstract β-thalassemias (β-thal) are a group of blood disorders caused by mutations in the β-globin gene (HBB) cluster. associates with α-globin to form adult hemoglobin (HbA, α2β2), main oxygen-carrier erythrocytes. When chains absent or limiting, free α-globins precipitate and damage cell membranes, causing hemolysis ineffective erythropoiesis. Clinical data show that severity β-thal correlates number inherited genes (HBA1 HBA2), deletions having beneficial effect for patients. Here, we...
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...
RNA interference (RNAi) has tremendous potential for investigating gene function and developing new therapies. However, the design validation of proficient vehicles stable safe microRNA (miR) small interfering (siRNA) delivery into relevant target cells remains an active area investigation. Here, we developed a lentiviral platform to efficiently coexpress one or more natural/artificial miR together with interest from constitutive regulated polymerase-II (Pol-II) promoters. By swapping...
Abstract The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 nuclease system has allowed the generation of disease models and development therapeutic approaches for many genetic non-genetic disorders. However, large genomic rearrangements raised safety concerns clinical application CRISPR/Cas9 approaches. Among these events, formation micronuclei chromosome bridges due to chromosomal truncations can lead massive localized one or few chromosomes. This phenomenon, known...
Leukodystrophies are rare diseases caused by defects in the genes coding for lysosomal enzymes that degrade several glycosphingolipids. Gene therapy leukodystrophies requires efficient distribution of missing CNS tissues to prevent demyelination and neurodegeneration. In this work, we targeted external capsule (EC), a white matter region enriched neuronal projections, with aim obtaining maximal protein from single injection site. We used bidirectional (bd) lentiviral vectors (LV) (bdLV)...
T-cell receptor (TCR) gene transfer for cancer immunotherapy is limited by the availability of large numbers tumor-specific T cells. TCR alpha and beta chains were isolated from a highly lytic HLA-A2-restricted cytotoxic lymphocyte (CTL) clone recognizing melanoma-associated Melan-A/MART-1 antigen inserted into lentiviral vector carrying bidirectional promoter capable robust coordinated expression two transgenes. Lentiviral vector-based delivery systems have shown increased efficiency...
Targeted genome editing has a great therapeutic potential to treat disorders that require protein replacement therapy. To develop platform independent of specific patient mutations, transgenes can be inserted in safe and highly transcribed locus maximize expression. Here, we describe an ex vivo approach achieve efficient gene targeting human hematopoietic stem/progenitor cells (HSPCs) robust expression clinically relevant proteins by the erythroid lineage. Using CRISPR-Cas9, integrate...