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公开(公告)号：US20240132964A1
公开(公告)日：2024-04-25
申请号：US18546611
申请日：2022-02-16
申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE , UNIVERSITÉ PARIS CITÉ , FONDATION IMAGINE , ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP)
IPC分类号： C12Q1/6883
CPC分类号： C12Q1/6883 , C12Q2600/118 , C12Q2600/158
摘要： SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, the inventors applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. This phenotype was associated with TNF-α signaling, sustained NF-κB signaling in monocytic/dendritic cells, alongside increased HIF-1α and VEGF signaling. Single-cell transcriptomic analyses identified
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公开(公告)号：US20230288414A1
公开(公告)日：2023-09-14
申请号：US18017249
申请日：2021-07-22
申请人： THE ROCKEFELLER UNIVERSITY , NSERM(Institut National de la Santé la Recherche Médicale) , Assistance Publique-Hôptiaux de Paris (APHP) , Université Paris Cité , Fondation Imagine
IPC分类号： G01N33/564
CPC分类号： G01N33/564 , G01N2800/52 , G01N2800/24 , G01N2333/555 , G01N2800/50
摘要： The present invention provides methods, assays and kits for assessment of patients positive for SARS-CoV-2 infection and methods of diagnosis and treatment of COVID-19 disease and for assessment and evaluation of individuals prior to vaccination with live attenuated virus vaccines, particularly including yellow fever vaccines and COVID-19 vaccines, to assess risk for vaccine-associated disease and adverse events, and for evaluation, treatment and management of patients who develop vaccine-associated disease. The invention provides methods and assays for identification and characterization of inborn errors of type I interferon immunity and also auto-antibodies against Type I IFNs that are associated with severe COVID-19 disease or that are correlated and linked with vaccine-associated disease. The invention further provides methods of diagnosing and determining altered response to or susceptibility to SARS-CoV-2 infection or to live attenuated virus vaccines and for applicable and suitable treatment of COVID-19 disease or vaccine-associated disease.
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公开(公告)号：US20230279438A1
公开(公告)日：2023-09-07
申请号：US17998603
申请日：2021-05-12
申请人： INSERM (Institut National de la Santé et la Recherche Médicale) , Université Paris Cité , Assistance Publique-Hôpitaux de Paris , Fondation Imagine
CPC分类号： C12N15/90 , C12N9/22 , C12N9/78 , C12N15/11 , C12Y305/04005 , C12N2310/20 , C12N2320/34
摘要： The clinical history of β-hemoglobinopathies shows that the severity is mitigated by the synthesis of the fetal γ-globin in adulthood, typically associated with genetic variants the HBB cluster known as hereditary persistence of fetal hemoglobin (HPFH) mutations. The inventors identified that most of the known HPFH mutations in the γ-globin promoters (C>T, G>A, T>C or A>G) can be recapitulated using CBE- and ABE-mediatedbase-editing approaches. In particular, the inventors designed gRNAs that, when combined with CBEs or ABEs, generate HPFH mutations, and either disrupt binding sites for transcriptional repressors (-200 and -115 sites) or generate de novo DNA motifs recognized by transcriptional activators (e.g., -198 T>C, the -175 T>C and -113 A>G). It is noteworthy that a subset of the gRNAs targeting the -200 and the 115 regions are predicted to generate simultaneously HPFH mutations and also to make base changes other than HPFH mutations in or around the LRF and BCL11A binding sites, which might further reduce LRF and BCL11A occupancy. Accordingly, the present invention relates to base editing approaches for the treatment of β-hemoglobinopathies.
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公开(公告)号：US11725183B2
公开(公告)日：2023-08-15
申请号：US16548280
申请日：2019-08-22
申请人： INSTITUT PASTEUR , FONDATION IMAGINE , ASSISTANCE PUBLIQUE—HOPITAUX DE PARIS , UNIVERSITE PARIS DESCARTES , INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (IN-SERM)
发明人： Gerard Eberl , David Bikard , Pamela Schnupf , Nadine Cerf Bensussan , Valerie Gaboriau-Routhiau , Philippe Sansonetti
CPC分类号： C12N1/20 , C12N13/00 , C12N15/74 , C12N2502/23
摘要： The present invention relates to an in vitro method of culturing a segmented filamentous bacterium strain, comprising co-culturing said segmented filamentous bacterium strain with a eukaryotic host cell, wherein the culture is performed at an O2 level inferior to 5% in a rich tissue culture liquid medium containing bacterial medium components including iron. The present invention also relates to methods for genetically modifying a segmented filamentous bacterium strain comprising a step a culturing the strain in vitro.
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公开(公告)号：US20230136699A1
公开(公告)日：2023-05-04
申请号：US17904124
申请日：2021-02-26
申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) , ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP) , FONDATION IMAGINE , UNIVERSITÉ PARIS CITÉ
发明人： Manuel SCHIFF , Marina CAVAZZANA , Pascale DE LONLAY-DEBENEY , Marcelo SIMON SOLA , Clément PONTOIZEAU , Chris OTTOLENGHI
摘要： Maple syrup urine disease (MSUD) is a rare autosomal recessive disease with an incidence that is caused by a defective activity of the branched-chain 2-keto acid dehydrogenase (BCKD) leading to accumulation of branched-chain amino acids (BCAA) leucine, isoleucine, valine and their corresponding alpha-ketoacids (BCKA) in tissues and body fluids. The inventors herein characterized the Bckdha−/− mouse and Bckdhb−/− mouse recapitulating the classical forms of MSUD. As a proof of concept, they developed a (liver-directed) AAV gene therapy based on the transfer of human BCKDHA (hBCKDHA) or BCKDHB (hBCKDHB) mediated by AAV8 during immediate neonatal period in Bckdha−/− or Bckdhb−/− mice. The inventors demonstrated that hBCKDHA gene transfer completely rescued the lethal early-onset phenotype of Bckdha−/− mice allowing long-term survival to age 12 months, at which they were systematically sacrificed, without overt phenotypic abnormalities. They also demonstrated that hBCKDHB gene transfer exhibited similar survival and a normal growth without overt phenotypic abnormalities at age 3 months, with a dramatic improvement of the biochemical phenotype. The present invention relates to a method of treating MSUD by gene therapy.
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6.发明申请公开(公告)号：US20210052546A1
公开(公告)日：2021-02-25
申请号：US16964781
申请日：2019-01-23
申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) , UNIVERSITE DE PARIS , FONDATION IMAGINE , ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP) , UNIVERSIDAD DE GRANADA
IPC分类号： A61K31/353 , A61P19/00
摘要： FGFR3-related chondrodysplasias represent a group of rare diseases. Among them, achondroplasia, a nonlethal form of chondrodysplasia, is the most common type of dwarfism. The mutation, which produce an increase of FGFR3 function, affects many tissues, most strikingly the cartilaginous growth plate and bone in the growing skeleton, leading to a variety of manifestations and complications. In attempt to find a new therapeutic approach for FGFR3-related chondrodysplasia, the inventors purified (−)-epicatechin from T. cacao and showed that (−)-epicatechin treatment significantly increases the length of the Fgfr3Y367C/+ femurs comparing to Fgfr3+/+ femurs and improves the whole growth plate cartilage. The present invention thus relates to the use of (−)-epicatechin for the treatment of FGFR3-related chondrodysplasias.
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公开(公告)号：US20200046767A1
公开(公告)日：2020-02-13
申请号：US16485488
申请日：2018-02-12
申请人： Assistance Publique - Hopitaux de Paris , Fondation Imagine - Institut des Maladies Génétiques , Université Paris Descartes , Institut National de la Santé et de la Recherche Médicale
发明人： Isabelle André , Marina Cavazzana , Kuiying Ma , John Tchen
IPC分类号： A61K35/17 , C12N5/0783
摘要： The invention relates to an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing TNF-alpha and/or an antagonist of the Aryl hydro-carbon/Dioxin receptor, in particular StemRegenin 1 (SR1), in presence of a Notch ligand and optionally a fibronectin fragment.
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公开(公告)号：US09377471B2
公开(公告)日：2016-06-28
申请号：US14547208
申请日：2014-11-19
申请人： Institut National de la Sante et de la Recherche Medicale (INSERM) , CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) , Universite Paris Descartes—Paris V , Assistance Publique—Hopitaux de Paris , Fondation Imagine
CPC分类号： C07K16/18 , A61K31/70 , A61K31/7088 , A61K38/02 , G01N33/5094 , G01N33/6893 , G01N33/80 , G01N2333/805 , G01N2500/02 , G01N2800/22
摘要： Methods and compositions for the treatment of β-thalassemia are provided. Methods and compositions restore or increase erythrocyte maturation in individuals afflicted with β-TM by preventing proteolysis of GATA-1 protein. Screening methods for identifying agents which bind heat shock protein 70 (HSP-70) and inhibit HSP-70 α-globin binding, but which allow GATA-1 protein-HSP-1 binding in a manner that prevents GATA-1 proteolysis.
摘要翻译： 提供了治疗“地中海贫血”的方法和组合物。 方法和组合物通过预防GATA-1蛋白的蛋白水解来恢复或增加患有'bgr-TM'的个体的红细胞成熟。 用于鉴定结合热休克蛋白70（HSP-70）并抑制HSP-70α-珠蛋白结合但允许以防止GATA-1蛋白水解的方式进行GATA-1蛋白-HSP-1结合的试剂的筛选方法。
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9.发明授权公开(公告)号：US11951090B2
公开(公告)日：2024-04-09
申请号：US16964781
申请日：2019-01-23
申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) , UNIVERSITE DE PARIS , FONDATION IMAGINE , ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP) , UNIVERSIDAD DE GRANADA
IPC分类号： A61K31/353 , A61P19/00
CPC分类号： A61K31/353 , A61P19/00
摘要： FGFR3-related chondrodysplasias represent a group of rare diseases. Among them, achondroplasia, a nonlethal form of chondrodysplasia, is the most common type of dwarfism. The mutation, which produce an increase of FGFR3 function, affects many tissues, most strikingly the cartilaginous growth plate and bone in the growing skeleton, leading to a variety of manifestations and complications. In attempt to find a new therapeutic approach for FGFR3-related chondrodysplasia, the inventors purified (−)-epicatechin from T. cacao and showed that (−)-epicatechin treatment significantly increases the length of the Fgfr3Y367C/+ femurs comparing to Fgfr3+/+ femurs and improves the whole growth plate cartilage. The present invention thus relates to the use of (−)-epicatechin for the treatment of FGFR3-related chondrodysplasias.
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公开(公告)号：US20240103019A1
公开(公告)日：2024-03-28
申请号：US18256453
申请日：2021-12-08
申请人： INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE , ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS , CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) , FONDATION IMAGINE , UNIVERSITÉ PARIS CITÉ , UNIVERSITE ANTILLES GUYANE , ETABLISSEMENT FRAN¿AIS DU SANG (EFS)
发明人： Thierry PEYRARD , Slim AZOUZI , Oliver HERMINE , Yves COLIN-ARONOVICZ , Romain DUVAL , Caroline LE VAN KIM
CPC分类号： G01N33/6893 , G01N33/80 , G01N2405/06 , G01N2440/38 , G01N2800/2857 , G01N2800/34
摘要： Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors more than 150 proteins to the cell surface. Pathogenic variants in several genes that participate in GPI biosynthesis cause inherited GPI deficiency (IGD) disorders. Here, the inventors reported that homozygous null alleles of PIGG, a gene involved in GPI modification, are responsible for the rare Emm-negative blood phenotype. Using a panel of K562 cells defective in both the GPI-transamidase and GPI remodeling pathways, they demonstrate that the Emm antigen, whose molecular basis has remained unknown for decades, is carried only by free GPI and that its epitope is composed of the second and third ethanolamine of the GPI backbone. Importantly, the inventors show that the decrease in Emm expression in several IGD patients is indicative of GPI defects. Overall, our findings establish Emm as a novel blood group system and have important implications for understanding the biological function of human free GPI.
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