Abstract: The present invention concerns the endonucleases capable of cleaving a target sequence located in a “safe harbor loci”, i.e. a loci allowing safe expression of a transgene. The present invention further concerns the use of such endonucleases for inserting transgenes into a cell, tissue or individual.

Abstract: An I-CreI variant, wherein one of the two I-CreI monomers has at least two substitutions, one in each of the two functional subdomains of the LAGLIDADG core domain situated respectively from positions 28 to 40 and 44 to 77 of I-CreI, said variant being able to cleave a DNA target sequence from the glutamine synthetase gene. Use of said variant and derived products for improving expression system for the production of recombinant protein.

Abstract: An I-CreI variant, wherein at least one of the two I-Cre1 monomers has at least two substitutions, one in each of the two functional subdomains of the LAGLIDADG core domain situated from positions 26 to 40 and 44 to 77 of I-CreI, said variant being able to cleave a DNA target sequence from the genome of a non-integrating virus, in particular herpes simplex virus (HSV) or Hepatitis B virus (HBV) for use in genome engineering and for in vivo and ex vivo (gene cell therapy) genome therapy as well as the treatment of a virus infection.

Abstract: The present invention concerns new modular base-per-base specific nucleic acid binding domains (MBBBD) derived from newly identified proteins from the bacterial endosymbiont Burkholderia Rhizoxinica and their use for engineering nucleic acid processing enzymes, such as specific endonucleases or transcription activators.

Abstract: Methods for improving or modulating targeting specificity of TALE proteins by introducing alternative RVDs into their modular nucleic acid binding domains. Polynucleotides encoding TALE proteins having alternative targeting specificity towards a nucleic acid target sequence. TALE proteins having alternative targeting specificity towards a nucleic acid target sequence and methods of making and using them.

Abstract: A method of expanding TCRalpha deficient T-cells by expressing pTalpha or functional variants thereof into said cells, thereby restoring a functional CD3 complex. This method is particularly useful to enhance the efficiency of immunotherapy using primary T-cells from donors. This method involves the use of pTalpha or functional variants thereof and polynucleotides encoding such polypeptides to expand TCRalpha deficient T-cells. Such engineered cells can be obtained by using specific rare-cutting endonuclease, preferably TALE-nucleases. The use of Chimeric Antigen Receptor (CAR), especially multi-chain CAR, in such engineered cells to target malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.

Abstract: A method for modulating double-strand break-induced mutagenesis at a genomic locus of interest in a cell, thereby giving new tools for genome engineering, including therapeutic applications and cell line engineering. A method for modulating double-strand break-induced mutagenesis, concerns the identification of effectors that modulate double-strand break-induced mutagenesis by use of interfering agents; these agents are capable of modulating double-strand break-induced mutagenesis through their respective direct or indirect actions on said effectors. Methods of using these effectors, interfering agents and derivatives, respectively, by introducing them into a cell in order to modulate and more particularly to increase double-strand break-induced mutagenesis. Specific derivatives of identified effectors and interfering agents, vectors encoding them, compositions and kits comprising such derivatives for modulating or increasing double-strand break-induced mutagenesis.

Abstract: An object of the invention is to provide a method and apparatus for the delivery of polynucleotide vaccines into mammalian skin cells to increase T cell response and to reduce pain and discomfort due to long electric waveform application and due to muscle contractions. The method for the delivery of polynucleotide vaccines into mammalian skin cells includes the steps of: (a.) administering a polynucleotide vaccine into the skin at an administration site, (b.) applying a needle electrode to the skin in the vicinity to the administration site, and (c.) applying a sequence of at least three single, operator-controlled, independently programmed, narrow interval electrical waveforms, which have pulse intervals that are less than 100 milliseconds, to deliver the polynucleotide vaccine into the skin cells by electroporation.

Abstract: The present invention relates to polypeptides and more particularly to Transcription Activator-Like Effector derived proteins that allow to efficiently target and/or process nucleic acids. The present invention also concerns methods to use these proteins. The present invention also relates to vectors, compositions and kits in which RVD domains and Transcription Activator-Like Effector (TALE) proteins of the present invention are used.

Abstract: The present invention relates to methods for developing engineered T-cells for immunotherapy that are non-alloreactive. The present invention relates to methods for modifying T-cells by inactivating both genes encoding T-cell receptor and an immune checkpoint gene to unleash the potential of the immune response. This method involves the use of specific rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells, which are available from donors or from culture of primary cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.

Abstract: A new I-CreI derived single-chain meganuclease comprising two domains, each domain comprising a portion of a parent I-CreI monomer which extends at least from the beginning of the first alpha helix to the end of the C-terminal loop and said two domains being joined by a peptidic linker which allows them to fold as a I-CreI dimer that is able to bind and cleave a chimeric DNA target comprising one different half of each parent homodimeric I-CreI meganuclease target sequence. Use of said I-CreI derived single-chain meganuclease for genetic engineering, genome therapy and antiviral therapy.

Abstract: Materials and methods are provided for making soybean varieties that have altered oil composition as a result of mutations in the FAD2-1A and FAD2-1B genes.

Abstract: The present invention concerns a method for modulating double-strand break-induced homologous recombination through the identification of effectors that modulate said double-strand break-induced homologous recombination by uses of interfering agents; these agents are capable of modulating double-strand break-induced homologous recombination through their respective actions on said effectors. The present invention also concerns the uses of these effectors and interfering agents and derivatives, respectively, by introducing them in an eukaryotic cell in order to modulate and more particularly to increase double-strand break-induced homologous recombination and gene targeting efficiency. The present invention also relates to specific derivatives of identified effectors and interfering agents, vectors encoding them, compositions and kits comprising such derivatives in order to modulate and more particularly to increase double-strand break-induced homologous recombination and gene targeting efficiency.

Abstract: The present invention relates to a method for the assembly and cloning of polynucleotides comprising highly similar polynucleotidic modules, that is highly versatile, does not require intermediate amplification step and can be easily automated for high throughput production of customized polynucleotidic modules.

Abstract: The present invention relates to a method for increasing double-strand-break induced mutagenesis at a genomic locus of interest in a cell, thereby giving new tools for genome engineering, including therapeutic applications and cell line engineering. More specifically, the present invention concerns the combined use of TALEN or meganucleases with TREX2, especially under the form of single-chain proteins.

Abstract: The present invention concerns new modular base-per-base specific nucleic acid binding domains (MBBBD) derived from newly identified proteins from the bacterial endosymbiont Burkholderia Rhizoxinica and their use for engineering nucleic acid processing enzymes, such as specific endonucleases or transcription activators.

Abstract: A novel population of multipotent cardiac precursor (MCP) cells derived from human blastocysts derived stem cells is disclosed, methods for the preparation thereof and use of the cells for in vitro testing. Basement cells derived from hBS cells are also disclosed and method for the preparation of MCP cells from basement cells. The MCP cells have the following characteristics i) at least 1% of the cells exhibit no antigen expression of one or more markers for undifferentiated cell, the marker being selected from the group consisting of SSEA-3, SSEA-4, TRA-1-60, TRA-1-81 and Oct-4, ii) at least 1% of the cells exhibit no protein expression of one or more of a neural marker including nestin or GFAP iii) at least 1% of the cells exhibit protein and/or gene expression of one or more of a mesodermal marker including brachyury, vimentin or desmin iv) at least 1% of the cells exhibit protein and/or gene expression of Flk-1 (KDR). Furthermore, the MCP cells have a characteristic morphology.

Abstract: The present invention relates to a method to treat a genetic disease in an individual caused by at least one frame shift or at least one non sense mutation in the human dystrophin gene comprising at least the step of bringing into contact at least one meganuclease enzyme, which recognizes and cuts a target site in the human dystrophin gene, with the genome of said individual under conditions wherein said at least one meganuclease recognizes and cleaves its target site in the human dystrophin gene. Said method applies also to a set of meganuclease enzymes, which each recognizes and cuts a different target site. The present invention also relates to a kit comprising, at least one meganuclease enzyme as defined above and medicament comprising said meganuclease.

Abstract: Meganuclease variants which cleave at least one target in the provirus of a retrovirus and in particular which cleave the genomic insertion of the provirus. The present invention particular relates to meganuclease variants which cleave the provirus of the Human Immunodeficiency Virus genome following genomic insertion. Vector encoding such variants, as well as to a cell or multi-cellular organism modified by such a vector and use of said meganuclease variants and derived products for genome engineering and for in vivo and ex vivo (gene cell therapy) genome therapy.

Abstract: Materials and methods are provided for making plants (e.g., Solanum varieties) with decreased accumulation of reducing sugars and acrylamide in cold-stored potatoes, specifically, by making TALE-nuclease-induced mutations in genes encoding vacuolar invertase.