Abstract: The present invention relates to a mini-glycogen debranching enzyme ((GDE); mini-GDE) for the treatment of glycogen storage disease III (GSDIII (Cori disease). Also disclosed are functional truncated human GDE polypeptides, functional non-human GDE polypeptides, nucleic acid molecules, nucleic acid constructs, or vectors encoding functional truncated human GDE or non-human GDE polypeptides as well as host cells expressing functional truncated human GDE or non-human GDE polypeptides. In a further aspect, the disclosure provides functional truncated human GDE polypeptides, functional non-human GDE polypeptides, nucleic acid molecules, nucleic acid constructs, vectors, or cells of the invention for use in a method for treating GSDIII (Cori disease).

Abstract: The invention relates to a hybrid AAV vector comprising a transgene of interest operably linked to an hepatocyte-specific promoter, which enhances transgene expression in the liver and its use for liver-directed gene therapy.

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.

Abstract: The invention relates to an immune cell engineered to express a chimeric antigen receptor (CAR) which specifically binds Fibroblast Activation Protein (FAP) for use in the treatment of skeletal muscle fibrosis in muscular dystrophies.

Abstract: The present invention concerns a quasidystrophin (QD) having the structure CH1CH2H1R1R2R3H2R8R9 in its N-terminal part and advantageously further comprising the R16 and R17 rod domains, as well as the dual AAV vector system which allows producing it.

Abstract: The present invention relates to compositions and methods for the delivery of therapeutic proteins to the CNS using recombinant AAV vectors. More specifically, the invention relates to compositions and methods for delivering proteins into the cerebrospinal fluid of mammalian subjects through peripheral administration of AAV vectors. The invention may be used to treat various disorders of the central nervous system, including degenerative diseases and motor neuron diseases.

Abstract: The invention relates to a nucleic acid construct for gene therapy of FGF-23 related hypophosphatemic diseases, in particular gene therapy directed to muscle, liver or hematopoietic tissue, more particularly liver tissue. The invention relates also to a vector comprising the nucleic acid construct, and their use for the treatment of FGF-23 related hypophosphatemic diseases, in particular XLH, by gene therapy.

Abstract: The present invention relates to hybrid transcription regulatory elements to drive gene expression, in particular hybrid promoters, designed by the fusion of at least two transcription regulatory elements with different tissue selectivity, such as two promoters driving expression in different tissues in a tissue-selective manner.

Abstract: A fluidic system for producing extracellular vesicles from producer cells, including at least one container, a liquid medium contained by the container and producer cells, characterised in that it also includes microcarriers suspended in the liquid medium, the majority of producer cells being adherent to the surface of the microcarriers, and a liquid medium agitator, the agitator and the dimensions of the container being adapted to control a turbulent flow of the liquid medium in the container.

Abstract: The invention relates to a recombinant adeno-associated virus (AAV) capsid protein, which is a hybrid between AAV serotype 9 (AAV9) and AAV serotype 74 (AAVrh74) capsid proteins, wherein said recombinant hybrid AAV capsid protein has a reduced liver tropism compared to the parent AAV9 and AAVrh74 capsid proteins. The invention relates also to the derived hybrid AAV serotype vector particles packaging a gene of interest and their use in gene therapy, in particular for treating neuromuscular genetic diseases.

Abstract: A fluidic system for producing extracellular vesicles from producer cells, including at least one container, a liquid medium contained by the container and producer cells, characterised in that it also includes microcarriers suspended in the liquid medium, the majority of producer cells being adherent to the surface of the microcarriers, and a liquid medium agitator, the agitator and the dimensions of the container being adapted to control a turbulent flow of the liquid medium in the container.

Abstract: The invention relates to a recombinant adeno-associated virus (AAV) capsid protein, which is a hybrid between AAV serotype 9 (AAV9) and AAV serotype 74 (AAVrh74) capsid proteins, wherein said recombinant hybrid AAV capsid protein has a reduced liver tropism compared to the parent AAV9 and AAVrh74 capsid proteins. The invention relates also to the derived hybrid AAV serotype vector particles packaging a gene of interest and their use in gene therapy, in particular for treating neuromuscular genetic diseases.

Abstract: A composition comprising a gene therapy product for use in the treatment of a dystrophic disease in a subject, advantageously in humans, wherein: the gene therapy product comprises a nucleic acid sequence encoding a functional microdystrophin; the composition is systemically administered.

Abstract: The invention relates to a peptide-modified AAV capsid with improved tropism, in particular increased muscle tropism and/or reduced liver tropism. The invention relates also to the derived recombinant AAV vector particle packaging a gene of interest, and its use in gene therapy, in particular for treating muscle diseases.

Abstract: The present invention relates to a genetically modified hematopoietic stem cell comprising, in at least one globin gene comprised in the genome thereof, at least one transgene encoding a therapeutic protein or a therapeutic ribonucleic acid, the said transgene being placed under the control of the endogenous promoter of the said globin gene.

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.

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.

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.

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.

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.