Press Release

Cellectis SA announces publication in Nucleic Acids Research of the generation of a novel hybrid meganuclease

Paris, France - June the 03^rd, 2003 - Cellectis SA, a biotechnology company specialized in rational genome engineering, announced today the publication, in Nucleic Acids Research, of data demonstrating that "a novel engineered meganuclease induces homologous recombination in yeast and mammalian cells".

"This is the first 100% Cellectis scientific publication" says Dr. Frédéric Pâques, CSO of Cellectis. "It represents a major step towards the use of custom made meganucleases for genome surgery"

In the wild, meganucleases are essentially represented by homing endonucleases. These proteins trigger the spreading of genetic mobile elements through targeted homologous recombination. The authors used different fusions of homing endonuclease of the LAGLIDADG family (the major and best characterized family) to obtain novel active proteins.

In one of these fusions, two I-CreI monomers have been linked in a single chain molecule. The natural I-CreI is functional as an homodimer. The novel protein cleaves its target in vitro, but also in yeast and mammalian cells, where it was shown to induce homologous recombination in extrachromosomal reporter systems.

The other fusion involves an I-DmoI moiety and an I-CreI monomer. As expected, it cleaves a novel DNA target, made of a half I-DmoI target and a half I-CreI target. As with the parental I-DmoI molecule, cleavage activity is observed at high temperature (65°C), and the activity could not be assayed in cells.

These results show that LAGLIDADG proteins are made of separable DNA binding domains that can be recombined. Since these proteins belong to the largest and best characterized family of homing endonucleases, domain swapping between such enzymes could provide a great number of novel proteins. Also, plasticity and modularity will be two essential features if directed molecular evolution strategies are to be used to obtain novel cleavage specificities.

The printed version of the paper is published this month, June 2003, on Nucleic Acids Research volume 31 issue 11, and can be accessed on line via the Nucleic Acids Research website at: http://nar.oupjournals.org.

Cellectis SA (www.cellectis.com) was founded in 1999, as a spin-off from the Institut Pasteur. It is the first company to apply the Meganuclease Recombination System approach to in vivo genome engineering. The company is developing Meganucleases that can target a unique DNA break in vivo, as a fundamentally enabling technology for commercial applications in human therapeutics, pharmaceutical discovery, agriculture, and industrial biotechnology.
As of today, Cellectis has entered into more than 15 deals via its genome engineering technologies, including with major pharmaceutical and agroscience companies.
Cellectis' team today consists of 35 people including 14 PhDs and the total invested capital since the company's inception is approximately EUR 20 million.

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