Abstract: The present invention relates to an expression system for systemic administration comprising a sequence encoding a protein, said expression system allowing: the expression at a therapeutically acceptable level of the protein in the target tissues including skeletal muscles; and the expression at toxically acceptable level of the protein in tissues other than the target tissues, especially in the heart.
Type:
Grant
Filed:
May 24, 2018
Date of Patent:
November 21, 2023
Assignees:
GENETHON, CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
Abstract: The present invention relates to compositions and methods, in particular to methods based on systemic injection of rAAV, for delivering genes to cells of the central nervous system in mammals, such as brain neurons or glial cells, and in particular to motor neurons or glial cells of the spinal cord The invention also relates to methods of treating motor neuron disorders in mammals by expression of therapeutic genes. The invention stems from the unexpected discovery that peripheral injection of AAV vectors leads to a bypass of the blood brain barrier and a massive infection of motor neurons. The invention may be used in any mammal, including human subjects.
Type:
Grant
Filed:
August 9, 2019
Date of Patent:
September 26, 2023
Assignees:
GENETHON, CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
Abstract: The invention relates to the treatment of dilated cardiomyopathies, in particular genetic dilated cardiomyopathies, using non-expressible inhibitors of the WNT pathway or TGF-? pathway, alone or in combination.
Type:
Application
Filed:
June 9, 2021
Publication date:
September 7, 2023
Applicants:
Genethon, Universite d'Evry Val d'Essonne, Institut National de la Santé et de la Recherche Médicale
Abstract: The invention relates to a composition for enhancing utrophin expression in cell by inducing mutations within a target sequence comprising a utrophin repressor binding site using a gene editing enzyme and the use thereof for the treatment of a dy-strophinopathy.
Type:
Application
Filed:
September 29, 2021
Publication date:
August 31, 2023
Applicants:
Genethon, Universite d'Evry Val d'Essonne, Institut National de la Santé et de la Recherche Médicale
Abstract: The invention relates to the treatment of genetic dilated cardiomyopathies using expressible modulators of the Wnt pathway or TGF-? pathway, preferably using gene transfer.
Type:
Application
Filed:
June 9, 2021
Publication date:
August 24, 2023
Applicants:
Genethon, Institut National de la Santé et de la Recherche Médicale, Universite d'Evry Val d'Essonne
Abstract: The invention relates to a method of preparation of a recombinant hybrid adeno-associated virus (AAV) capsid protein with improved tropism and to the recombinant hybrid AAV capsid protein obtainable by the method. The invention relates also to the derived expression vector, modified cell, and hybrid capsid AAV vector particle packaging a gene of interest, and its use in tissue-targeted gene therapy for treating various diseases.
Type:
Application
Filed:
July 5, 2021
Publication date:
August 3, 2023
Applicants:
Genethon, Institut National de la Santé et de la Recherche Médicale, Universite d'Evry Val d'Essonne
Abstract: The invention relates to the use of a recombinant porcine adeno-associated virus (AAV) vector comprising a peptide-modified porcine AAV serotype 1 (AAVpol) capsid in gene therapy of muscle and/or central nervous system (CNS) disorders, in particular neuromuscular diseases such as genetic neuromuscular diseases.
Type:
Application
Filed:
April 28, 2021
Publication date:
June 8, 2023
Applicants:
Genethon, Universität Heidelberg, Universite d'Evry val d'Essonne, Institut National de la Santé et de la Recherche Médicale
Inventors:
Ana Buj Bello, Edith Renaud-Gabardos, Dirk Grimm, Jonas Weinmann
Abstract: The present invention concerns synthetic polynucleotides encoding a human fukutin-related protein (FKRP) wherein the synthetic polynucleotides contain at least a mutation avoiding supplementary transcript(s) generated from frameshift start codon(s). The synthetic polynucleotides are useful, especially for treating a pathology linked to a FKRP deficiency or induced by a defect in ?-dystroglycan (?-DG) glycosylation, such as LGMD2I.
Type:
Grant
Filed:
July 6, 2018
Date of Patent:
March 7, 2023
Assignees:
GENETHON, UNIVERSITE D'EVRY-VAL-D'ESSONNE, INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE)
Inventors:
Isabelle Richard, Evelyne Gicquel-Zouida, William Lostal
Abstract: The present invention provides compositions and methods for treating a myopathy. In certain embodiments, the invention provides compositions and methods for treating, improving muscle function, and prolonging survival in a subject with X-linked myotubular myopathy (XLMTM). The present invention provides a method comprising systemic administration of a composition that induces the increased expression of myotubularin in the muscle of a subject. The invention provides sustained regional and global increases in muscle function.
Type:
Grant
Filed:
December 28, 2017
Date of Patent:
January 31, 2023
Assignees:
Wake Forest University Health Sciences, Genethon, Children's Medical Center Corporation
Inventors:
Martin K. Childers, Alan H. Beggs, Ana Maria Buj Bello
Abstract: The present invention concerns the use of antisense oligonucleotides (AON) capable of inhibiting expression of dynamin 2, advantageously human dynamin 2, for use in the treatment of Charcot-Marie-Tooth disease (CMT) and centronuclear myopathies (CNM).
Type:
Grant
Filed:
April 10, 2018
Date of Patent:
November 15, 2022
Assignees:
GENETHON, UNIVERSITE D'EVRY-VAL-D'ESSONNE, INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE)
Abstract: The present invention relates to a method for treating a Leber congenital amaurosis in a patient harbouring the mutation c.2991+1655 A>G in the CEP290 gene, comprising the step of administering to said patient at least one antisense oligonucleotide complementary to nucleic acid sequence that is necessary for preventing splicing of the cryptic exon inserted into the mutant c. 2991+1655 A>G CEP290 mRNA.
Type:
Grant
Filed:
March 3, 2020
Date of Patent:
November 8, 2022
Assignees:
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE, CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS), GENETHON, UNIVERSITE PARIS DESCARTES, ENSCP—CHIMIE PARISTECH—ECOLE NATIONALE SUPERIEURE DE CHIME DE PARIS, ASSISTANCE PUBLIQUE—HOPITAUX DE PARIS
Inventors:
Jean-Michel Rozet, Antoine Kichler, Isabelle Perrault, Josseline Kaplan, Xavier Gerard, Daniel Scherman, M. Arnold Munnich
Abstract: Adeno-associated virus (AAV) is a defective mono-stranded DNA virus, endemic in human population (35-80%). Recurrent clonal AAV2 insertions are associated with the pathogenesis of rare human hepatocellular carcinoma (HCC) developed on normal liver. The aimed of the inventors was to characterize the natural history of AAV infection in the liver. Viral DNA was thus quantified in tumor and non-tumor liver tissues of 1461 patients. Presence of episomal form and viral mRNA expression were analyzed using a DNAse/TaqMan based assay and quantitative RT-PCR. In silico analyses using viral capture data explored viral variants and new clonal insertions. AAV DNA was detected in 21% of the patients equally distributed in 2 major viral subtypes: one similar to AAV2, the other hybrid between AAV2 and AAV13 sequences. Thus the inventors provided an integrated analysis of the wild type AAV infection in the liver with the identification of viral genotypes, molecular forms, helper virus relationship and viral integrations.
Type:
Application
Filed:
April 23, 2020
Publication date:
September 8, 2022
Applicants:
Institut National de la Santé et de la Recherche Médicale, Assistance Publique-Hôpitaux de Paris, Genethon, Sorbonne Université, Universite de Paris, Université d'Evry-Val-d'Essonne, Universite Paris XIII Paris-Nord Villetaneuse
Inventors:
Jessica Zucman-Rossi, Jean-Charles Nault, Tiziana La Bella, Giuseppe Ronzitti, Sandrine Imbeaud, Patrice Vidal
Abstract: An RNA interference (RNAi) strategy is provided based on use of artificial microRNA (amiR) to reduce NKCC1 expression. In particular, a method is provided that achieves neuron-specific expression of specific amiR against NKCC1 by using a human Synapsin promoter to drive transgene expression.
Type:
Grant
Filed:
April 11, 2018
Date of Patent:
August 30, 2022
Assignees:
INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE, UNIVERSITE D'EVRY-VAL-D'ESSONNE, GENETHON, FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA, FONDAZIONE TELETHON
Inventors:
Federico Mingozzi, Giuseppe Ronzitti, Andrea Contestabile, Laura Cancedda
Abstract: The present invention relates to variants of acid-alpha glucosidase and uses thereof. Said variants are sequence-optimized and/or are linked to a heterogenous signal peptide.
Type:
Grant
Filed:
September 12, 2017
Date of Patent:
August 23, 2022
Assignees:
GENETHON, SORBONNE UNIVERSITÉ, DUKE UNIVERSITY
Inventors:
Federico Mingozzi, Giuseppe Ronzitti, Dwight D. Koeberl, Sang-Oh Han
Abstract: The invention relates to a recombinant adeno-associated virus (AAV) capsid protein, which is a peptide-modified hybrid between AAV serotype 9 (AAV9) and AAV serotype 74 (AAVrh74) capsid proteins comprising at least one copy of a peptide comprising the RGD motif, wherein said recombinant peptide-modified hybrid AAV capsid protein has a further reduced liver tropism and an increased muscle transduction compared to the recombinant hybrid AAV capsid protein not having said peptide. The invention relates also to the derived peptide-modified hybrid AAV serotype vector particles packaging a gene of interest and their use in gene therapy, in particular for treating neuromuscular genetic diseases, in particular muscular genetic diseases.
Type:
Application
Filed:
October 4, 2019
Publication date:
July 21, 2022
Applicants:
Genethon, Institut National de la Sante et de la Recherche Medicale, Universite d'Evry Val d'Essonne, Sorbonne Universite, Association Institut de Myologie
Inventors:
Giuseppe RONZITTI, Patrice VIDAL, Federico MINGOZZI