Cellectis

Cellectis S.a.

Jean-Charles Epinat

Philippe Duchateau

Emmanuel Lacroix

Patrick Chames

Sylvain Arnould

Frederic Paques

Julien Valton

Alexandre Juillerat

Jean-Pierre Cabaniols

Claudia Bertonati

George H Silva

Andre Choulika

David Sourdive

Marine Beurdeley

Phillippe Duchateau

Julianne Smith

Agnes Gouble

André Choulika

Christophe Perez-Michaut

Frédéric Paques

Agnès Gouble

Sylvia Bruneau

Fayza Daboussi

George Silva

The invention pertains to the field of adaptive cell immunotherapy. It aims at reducing the occurrence of translocations and cell deaths when several specific endonuclease reagents are used altogether to genetically modify primary immune cells at different genetic loci. The method of the invention allows to yield safer immune primary cells harboring several genetic modifications, such as triple or quadruple gene inactivated cells, from populations or sub-populations of cells originating from a single donor or patient, for their subsequent use in therapeutic treatments.

Sequential gene editing in primary immune cells

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 the DNA target sequence. The present invention also relates to compact TALENs, vectors, compositions and kits used to implement the method.

Method for the generation of compact tale-nucleases and uses thereof

The present invention relates to new Transcription Activator-Like Effector proteins and more particularly new Transcription Activator-Like Effector Nucleases (TALENs) that can efficiently target and process nucleic acids. The present invention also concerns methods to use these new Transcription Activator-Like Effector proteins. The present invention also relates to vectors, compositions and kits in which Transcription Activator-Like Effector proteins of the present invention are used.

Tale-protein scaffolds and uses thereof

The invention provides engineered diatoms and methods of producing oil using diatoms. The invention also provides methods of modifying the lipids quantity and/or quality produced by diatom organisms through genome engineering. Also provided are oils, fuels, oleochemicals, chemical precursors, and other compounds manufactured from such modified diatoms.

Modified diatoms for biofuel production

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.

Method for the generation of compact TALE-nucleases and uses thereof

Use of meganucleases for cleaving DNA in a non-human or an isolated human cell and, in some instances, inducing homologous recombination in said cells and to its application for genome engineering and gene therapy.

Use of meganucleases for inducing homologous recombination ex vivo and in toto in vertebrate somatic tissues and application thereof

A monomer of an I-CreI meganuclease variant wherein said monomer comprises mutations in the amino acid sequence of SEQ ID NO: 34, wherein said mutations include, (i) at least one and up to five amino acid substitutions from residue Q44 to residue R70, said substitutions selected from the group consisting of substitutions at positions Q44, T46, Y66, R68 and R7; and (ii) at least one and up to six amino acid substitutions from residue Q26 to residue Q38 said substitutions selected from the group consisting of substitutions at positions Q26, K28, N30, S32, Y33 and Q38, and wherein said monomer when in dimeric form binds and cleaves a DNA target sequence. Said dimeric forms include homodimeric, heterodimeric and single-chain I-CreI meganuclease variants.

The present invention relates to a polynucleotide encoding a monomer of an I-CreI variant said monomer comprising mutations in the amino acid sequence of SEQ ID NO: 34, wherein said mutations include: (i) at least one and up to eleven amino acid substitutions from residue S22 to Q44 said substitutions selected from the group consisting of substitutions at positions I24, Q26, K28, N30, S32, Y33, Q38, S40 and T42; and (ii) at least one and up to six amino acid substitutions from residue Y66 to I77 said substitutions selected from the group consisting of substitutions at positions Y66, R68, R70, V73 and I77; and wherein said monomer when in dimeric form binds and cleaves DNA.

I-DmoI derivatives with enhanced cleavage activity at 37&#xb0; 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.

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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.

Hybrid and single chain meganucleases and use thereof

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.

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Paris, France

Jean-Charles Epinat