Abstract: The invention provides cell penetrating peptide-nucleic acid conjugates having the formula P-L-N, wherein P is a cell penetrating peptide, N is a nucleic acid, preferably an oligonucleotide and more preferably a siRNA, and L is a hydrophilic polymer, preferably a polyethylene glycol (PEG)-based linker linking P and N together. Compositions, methods of use and methods for producing such conjugates are also disclosed.

Abstract: The present invention relates to a method for the generation of compact Transcription Activator-Like Effector Nucleases (TALENs) that can efficiently target and process double-stranded DNA. More specifically, the present invention concerns a method for the creation of TALENs that consist of a single TALE DNA binding domain fused to at least one catalytic domain such that the active entity is composed of a single polypeptide chain for simple and efficient vectorization and does not require dimerization to target a specific single double-stranded DNA target sequence of interest and process DNA nearby said DNA target sequence. The present invention also relates to compact TALENs, vectors, compositions and kits used to implement the method.

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 (SEQ ID NO: 150) core domain situated respectively from positions 26 to 40 and 44 to 77 of I-CreI, said variant being able to cleave a DNA target sequence from the mouse ROSA26 locus. Use of said variant and derived products for the engineering of transgenic mice and recombinant mouse cell lines expressing an heterologous protein of interest.

Abstract: The invention relates to an anti-bacterial composition, especially for controlling gram-negative bacteria, containing a combination of: a) at least one peptide of between 10 and 25 amino acid residues comprising: i) two positively charged domains with a neutral pH consisting of between 3 and 9 amino acid residues, at least two thirds thereof being cationic amino acids, ii) a group of two to three non-cationic amino acid residues located between said positively charged domains, iii) a group of between 0 and 10, preferably between 0 and 5, amino acid residues selected from the group comprising non-hydrophobic amino acids and positively charged amino acids, located at one of the terminal ends N or C of the peptide, a positively charged amino acid residue, however, not being directly adjacent to the positively charged domains; and b) at least one anti-bacterial compound.

Abstract: An object of the invention is to provide methods and compositions relating to a vaccine against prostate cancer which includes a non-human-primate PSA for administration to humans to provide an immune response against human PSA. More generally, an object of the invention is to provide methods and compositions relating to using a non-human primate xenogeneic antigen (e.g. protein) in a human, wherein, with respect to the non-human primate xenogeneic antigen that is used, there are relatively few interspecies differences between the non-human primate xenogeneic antigen and the human self antigen in order to induce an optimal immune response in the human to its native self antigen.

Abstract: I-DmoI derivatives with enhanced cleavage activity at 37° C., said mutant comprising a sequence of a mutant of a I-DmoI endonuclease or a chimeric 5 derivative thereof including at least the first I-DmoIdomain, said sequence comprising the sub-situation of at least: (i) one of the residues in positions 4, 20, 49, 52, 92, 94 and/or 95 of said first I-DmoIdomain, and/or (ii) one of the residues in positions 101, 102, and/or 109 of the linker or the beginning of the second domain of I-DmoI, if present. 10 Polynucleotide encoding said derivatives, cell, animal or plant comprising said polynucleotide and use thereof for isolating meganucleases with new DNA target specificity.

Abstract: This patent application relates to hybrid and/or single-chain rare-cutting endonucleases, called meganucleases, which recognize and cleave a specific nucleotide sequence, to polynucleotide sequences encoding for said rare-cutting endonucleases, to a vector comprising one of said polynucleotide sequences, to a cell or animal comprising one of said polynucleotide sequences or said rare-cutting endonucleases, to a process for producing one of said rare-cutting endonucleases and any use of the disclosed products and methods. More particularly, this invention contemplates any use of such rare-cutting endonuclease for genetic engineering and gene therapy.

Abstract: The present invention concerns a chimeric polypeptide comprising: (i) a first domain comprising an amino-acid sequence facilitating active transport across a biological membrane by the binding to an glycosaminoglycan, which is selected from the group consisting of a) (XBBBXXBX)n; (XBBXBX)n; c) (BBXmBBXp)n; d) (XBEXXTBX)n; e) (BXmBB)n; f) (BmXX)n or g) an antibody fragment, wherein each B is independently a basic amino acid preferably lysine or arginine; each X is independently a non-basic amino acid preferably hydrophobic amino acid; each m is independently an integer from zero to five; each n is independently an integer between one and ten; and each p is independently an integer between zero to five; and (ii) a second domain comprises an anti-activated RAS neutralizing antibody, fragment or derivative thereof; a polynucleotide encoding said polypeptide; a pharmaceutical composition comprising said polynucleotide or said polypeptide; and the use of said polypeptide for the manufacture of a medicament for trea

Abstract: The invention relates to a set of genetic constructs which allow the efficient and reproducible introduction of a specific nucleotide sequence at a fixed position in the genome by generating a double strand break at a specific position in the genome using a meganuclease and so stimulating a homologous recombination event at this locus between the genomic site and a transfected donor sequence. The present invention also relates to methods using these constructs and to these materials in the form of a kit.

Abstract: An 1-Cre1 variant, wherein one of the two 1-Cre1 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 1-Cre1, 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: The invention concerns an amino acid sequence capable of facilitating penetration of a substance of interest into cells and/or cell nuclei, characterized in that it is capable of reacting in vivo with aminoglycans. Optionally the sequence is derived from a protein of human origin.

Abstract: The current invention relates to polypeptides encoding mutant I-DmoI derivatives with enhanced cleavage activity and altered sequence specificity and uses of these polypeptides. These polypeptides comprise at least the first I-DmoI domain, and the peptide sequence comprises the substitution of at least one of residues 15, 19 and/or 20 as well as at least one of the residues in positions 27, 29, 33, 35, 37, 75, 76, 77, 81 of the first I-DmoI domain.

Abstract: Heterodimeric meganuclease comprising two domains of different meganucleases which are in two separate polypeptides, said heterodimeric meganuclease being able to cleave a chimeric DNA target sequence comprising one different half of each parent meganuclease DNA target sequence. Use of said herodimeric meganuclease and derived products for genetic engineering, genome therapy and antiviral therapy.

Abstract: Method of preparing 1-CreI meganuclease variants having a modified cleavage specificity, variants obtainable by said method and their applications either for cleaving new DNA target or for genetic engineering and genome engineering for non-therapeutic purposes. Nucleic acids encoding said variants, expression cassettes comprising said nucleic acids, vectors comprising said expression cassettes, cells or organisms, plants or animals except humans, transformed by said vectors.

Abstract: An I-MsoI homing endonuclease variant able to cleave mutant I-MsoI sites having variation at positions ±8 to ±10, a vector encoding said variant, a cell, an animal or a plant modified by said vector. Use of said I-MsoI endonuclease variant and derived products for genetic engineering, genome therapy and antiviral therapy.

Abstract: A single chain homing endonuclease, comprising a first variant of I-CreI having the amino acid sequence of accession number pdb 1g9y (SEQ ID NO: 23 is residues 1-153 of pdb Ig9y) and a second variant of I-CreI variant having the amino acid sequence of accession number pdb 1g9y (SEQ ID NO: 23 is residues 1-153 of pdb Ig9y) in a single polypeptide.

Abstract: A method for enhancing the cleavage activity of an I-CreI derived meganuclease, comprising the site-specific mutation of at least one amino acid residue which is selected in the group consisting of: the glycine at position 19, the phenylalanine at position 54, the phenylalanine at position 87, the serine at position 79, the valine at position 105 and the isoleucine at position 132 of I-CreI, and its application for the manufacturing of meganuclease cleaving a DNA target of interest, for use in genome therapy (treatment of genetic diseases) and genome engineering (making of transgenic animals, transgenic plants and recombinant cell lines).

Abstract: The present invention concerns a method for in vivo generation of a linear polynucleotide with 5? and 3? free ends from a vector having no free end, said linear polynucleotide being integrated into the host cell genome. The vector having no free end according to the present invention comprise the polynucleotide to be linearized or excised flanked by a cleavage site, said cleavage site being preferably not found in the host cell genome. The present invention also relates to the resulting cells and their uses, for example for production of proteins or other genes, biomolecules, biomaterials, transgenic plants, vaccines, transgenic animals or for treatment or prophylaxis of a condition or disorder in an individual.