Abstract: A method of targeting to the synovial tissue biodegradable drug delivery compositions or morselizing biodegradable drug delivery compositions are described. The biodegradable drug composition comprises a triblock copolymer containing a polyester and a polyethylene glycol and a diblock copolymer containing a polyester and an end-capped polyethylene glycol, as well as at least one pharmaceutically active principle is disclosed.

Abstract: A method of targeting to the synovial tissue biodegradable drug delivery compositions or morselizing biodegradable drug delivery compositions are described. The biodegradable drug composition comprises a triblock copolymer containing a polyester and a polyethylene glycol and a diblock copolymer containing a polyester and an end-capped polyethylene glycol, as well as at least one pharmaceutically active principle is disclosed.

Abstract: The present invention provides a pharmaceutical composition comprising: a biodegradable multi-branched copolymer comprising at least three polyester arms attached to a central core which comprises a polyether, and wherein the multi-branched copolymer is substantially insoluble in aqueous solution, further comprising at least one pharmaceutically active ingredient.

Abstract: A method of targeting to the synovial tissue biodegradable drug delivery compositions or morselizing biodegradable drug delivery compositions are described. The biodegradable drug composition comprises a triblock copolymer containing a polyester and a polyethylene glycol and a diblock copolymer containing a polyester and an end-capped polyethylene glycol, as well as at least one pharmaceutically active principle is disclosed.

Abstract: A method of targeting to the synovial tissue biodegradable drug delivery compositions or morselizing biodegradable drug delivery compositions are described. The biodegradable drug composition comprises a triblock copolymer containing a polyester and a polyethylene glycol and a diblock copolymer containing a polyester and an end-capped polyethylene glycol, as well as at least one pharmaceutically active principle is disclosed.

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: 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: An I-CreI variant, wherein at least 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 26 to 40 and 44 to 77 of I-CreI, said variant being able to cleave a DNA target sequence from the human IL2RG gene. Use of said variant and derived products for the prevention and the treatment of X-linked severe combined immunodeficiency.

Abstract: The present invention relates to 1-Cre1 variants which can in particular recognise and cleave DNA targets which do not comprise the same nucleotides at positions ±6 and ±7 which are present in the wild type 1-Cre1 target. The present invention also relates to 1-Cre1 variants which can recognise and cleave targets which do not comprise the wild type nucleotides at positions ±4, ±5, ±6, ±7 and to 1-Cre1 variants with new specificity which can recognise and cleave targets which do not comprise the wild type nucleotides at positions ±4, ±5, ±6, ±7, ±8, ±9 and ±10.

Abstract: An I-CreI variant, wherein one of the 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 26 to 40 and 44 to 77 of I-CreI, said variant being able to cleave a DNA target sequence from a RAG gene. Use of said variant and derived products for the prevention and the treatment of a SCID syndrome associated with a mutation in a RAG gene.

Abstract: A method for inducing a site-specific modification in the HPRT gene, for a non-therapeutic purpose, by contacting a DNA target sequence selected from the group consisting of the sequences SEQ ID NO: 1 to 14 thereby cleaving the DNA target with an I-CreI variant or single-chain derivative having at least one substitution in one of the two functional subdomains of the LAGLIDADG (SEQ ID NO: 153) core domain situated from positions 26 to 40 and 44 to 77 of I-CreI.

Abstract: Method to generate and select a meganuclease having at least two altered characteristics in comparison to a parent meganuclease, comprising the steps: a. constructing from a parent meganuclease, a first series of variants which differ from said parent meganuclease by at least one acid amino substitution; b. screening the variants from said first series of step a. and selecting those which have a first altered characteristic; c. constructing from the selected variants of step b. a second series of variants having a least one other amino acid substitution; d. screening the variants from said series of step b. and selecting those which have said first altered characteristic and a second altered characteristic. Polypeptide obtained from said method.

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: 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: An I-CreI variant, wherein at least 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 26 to 40 and 44 to 77 of I-CreI, said variant being able to cleave a DNA target sequence from the human IL2RG gene. Use of said variant and derived products for the prevention and the treatment of X-linked severe combined immunodeficiency.

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 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: An obligate heterodimer meganuclease consisting of a first and a second monomer, deriving from two different homodimeric LAGLIDADG (SEQ ID NO: 66) endonuclease monomers (parent monomers), and having at least one pair of mutations interesting corresponding residues of said parent monomers which make an intermolecular interaction between the two monomers of each parent homodimeric LAGLIDADG (SEQ ID NO: 66) endonuclease, a vector encoding said meganuclease, a cell, an animal or a plant modified by said vector and the use of said meganuclease and derived products for molecular biology, genome engineering and genome therapy.

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: An I-CreI variant or a single-chain derivative having at least one substitution in one of the two functional subdomains of the LAGLIDADG (SEQ ID NO: 153) core domain situated from positions 26 to 40 and 44 to 77 of I-CreI, and being able to cleave a DNA target sequence from the HPRT gene having a nucleotide sequence of SEQ ID NO: 1 to 14. Use of said variant for inducing a site-specific modification in the HPRT gene, for therapeutic (gene therapy of Lesch-Nyhan syndrome) or non-therapeutic purpose (engineering of transgenic animals and recombinant cell lines).