Approches génétiques intégrées et nouvelles thérapies pour les maladies rares

Présentation du laboratoire

"INTEGRARE" (Approches génétiques intégrées et nouvelles thérapies pour les maladies rares, UMR_S951) est une unité de recherche spécialisée dans la recherche de transfert et dans la thérapie génique des maladies génétiques rares. L’unité s’intéresse principalement aux myopathies, maladies métaboliques, maladies du sang ou déficits immunitaires. Utilisant des vecteurs viraux recombinants (AAV et vecteurs lentiviraux) ou les technologies CRISPR, les travaux de recherche visent à concevoir des approches thérapeutiques, définir les paramètres pharmacologiques et la sécurité des approches, et à lever les verrous notamment pour éviter les réponses immunitaires au traitement de thérapie génique.

Les candidats thérapeutiques prometteurs sont développés vers la clinique à travers les programmes thérapeutiques de Généthon. Plusieurs essais cliniques de thérapie génique sont actuellement en cours.

INTEGRARE est un partenariat entre Généthon, (une organisation privée de R et D créée par l’AFM/Téléthon), l'Inserm et les Universités (Université d'Evry / Université Paris Saclay, EPHE).

Les 20 dernières publications

Titre Auteurs Date de publication Source
Role of Regulatory T Cell and Effector T Cell Exhaustion in Liver-Mediated Transgene Tolerance in Muscle Isabelle Richard, Jérôme Poupiot, Pasqualina Colella, ... 13/12/2019 Molecular Therapy - Methods and Clinical Development
Biosafety Studies of a Clinically Applicable Lentiviral Vector for the Gene Therapy of Artemis-SCID Sabine Charrier, Fulvio Mavilio, Anne Galy, ... 13/12/2019 Molecular Therapy - Methods and Clinical Development
One vector to rule them all Giuseppe Ronzitti 04/12/2019 Science Translational Medicine
Identification of thiostrepton as a pharmacological approach to rescue misfolded alpha-sarcoglycan mutant proteins from degradation Isabelle Richard, Nathalie Bourg, Sara F. Henriques, ... 01/12/2019 Scientific Reports
Vectofusin-1 Improves Transduction of Primary Human Cells with Diverse Retroviral and Lentiviral Pseudotypes, Enabling Robust, Automated Closed-System Manufacturing Anne Galy, Mirella Mormin 01/12/2019 Human Gene Therapy
Titin splicing regulates cardiotoxicity associated with calpain 3 gene therapy for limb-girdle muscular dystrophy type 2A Guillaume Corre, Isabelle Richard, Carinne Roudaut, ... 27/11/2019 Science Translational Medicine
Deep morphological analysis of muscle biopsies from type III glycogenesis (GSDIII), debranching enzyme deficiency, revealed stereotyped vacuolar myopathy and autophagy impairment Federico Mingozzi, Louisa Jauze, Giuseppe Ronzitti, ... 28/10/2019 Acta Neuropathologica Communications
Challenges of Gene Therapy for the Treatment of Glycogen Storage Diseases Type i and Type III Louisa Jauze, Giuseppe Ronzitti 01/10/2019 Human Gene Therapy
Toward a scalable purification protocol of GaLV-TR-pseudotyped lentiviral vectors Anne Galy, Mirella Mormin 01/10/2019 Human Gene Therapy Methods
Functional and cellular localization diversity associated with Fukutin-related protein patient genetic variants Isabelle Richard, Evelyne Gicquel, Sara F. Henriques, ... 01/10/2019 Human Mutation
Temporary Reduction of Membrane CD4 with the Antioxidant MnTBAP Is Sufficient to Prevent Immune Responses Induced by Gene Transfer Guillaume Corre, Anne Galy, Jérémie Cosette, ... 13/09/2019 Molecular Therapy - Methods and Clinical Development
Real-Time Monitoring of Exosome Enveloped-AAV Spreading by Endomicroscopy Approach: A New Tool for Gene Delivery in the Brain Federico Mingozzi, Giuseppe Ronzitti, F. Collaud 13/09/2019 Molecular Therapy - Methods and Clinical Development
Immune-orthogonal orthologs: The solution for genome editing? Giuseppe Ronzitti 14/08/2019 Science Translational Medicine
Prevalence and long-term monitoring of humoral immunity against adeno-associated virus in Duchenne Muscular Dystrophy patients Federico Mingozzi, Christian Leborgne, Severine Charles, ... 01/08/2019 Cellular Immunology
Alpha-1-Antitrypsin Promoter Improves the Efficacy of an Adeno-Associated Virus Vector for the Treatment of Mitochondrial Neurogastrointestinal Encephalomyopathy Federico Mingozzi 01/08/2019 Human Gene Therapy
Liver-directed gene therapy results in long-term correction of progressive familial intrahepatic cholestasis type 3 in mice Giuseppe Ronzitti 01/07/2019 Journal of Hepatology
An AAV-SGCG Dose-Response Study in a γ-Sarcoglycanopathy Mouse Model in the Context of Mechanical Stress Daniel Stockholm, Guillaume Corre, Isabelle Richard, ... 14/06/2019 Molecular Therapy - Methods and Clinical Development
Dual muscle-liver transduction imposes immune tolerance for muscle transgene engraftment despite preexisting immunity Federico Mingozzi, Isabelle Richard, Pasqualina Colella, ... 06/06/2019 JCI Insight
Ca <sup>2+</sup> -induced sarcoplasmic reticulum Ca <sup>2+</sup> release in myotubularin-deficient muscle fibers Ana Buj-Bello 01/06/2019 Cell Calcium
Tailoring the CRISPR system to transactivate coagulation gene promoters in normal and mutated contexts Matteo Bovolenta, Elena Barbon 01/06/2019 Biochimica et Biophysica Acta - Gene Regulatory Mechanisms