Press Release

Cellectis SA reports method for the selection of novel engineered meganucleases in Nucleic Acids Research

Romainville, France - November the 23^rd, 2005 - Cellectis SA, a biotechnology company specialized in rational genome engineering, announced today the publication, in Nucleic Acids Research, of a method for the selection of novel, engineered meganucleases. In this article, entitled "In vivo selection of engineered homing endonucleases using double strand break induced homologous recombination", the authors describe selection procedures that rely on a cell based assay in the yeast Saccharomyces cerevisiae. This report can be found online at: nar.oxfordjournals.org.

The use of rare-cutting double-stranded DNA endonucleases, called meganucleases, has emerged as the most successful means to enhance gene targeting. The use of I-SceI (intron-encoded endonuclease I from Saccharomyces cerevisiae), has rapidly become a standard strategy. Significant efforts are being made to find, design or engineer new endonucleases with desired cleavage specificities. Different approaches have been undertaken by several teams to reach this goal, including construction of hybrid proteins, and screening or selection-based techniques. These techniques have been essentially based on bacterial genetic selection systems that link either DNA cleavage or DNA binding to cell survival or growth. The method described in this article is based on the selection of cleavage-induced recombination events in the yeast Saccharomyces cerevisiae. The use of eukaryotic cells is one advantage of this method over previous ones, in addition to the selection for chromosomal DNA rearrangements instead of DNA cleavage or binding. This method selects efficiently for novel functional endonucleases, with enrichment in the 10⁵ range per single run, and compares favorably to phage display in terms of output diversity. Combined with a High Throughput Screening strategy that relies on a similar cell-based assay, it will significantly enhance the potential to engineer novel tailored meganucleases for genome engineering applications (The HTS procedure is described in another publication, presently in press in Journal of Molecular Biology).

Cellectis SA (www.cellectis.com) was founded in 2000, as a spin-off from the Institut Pasteur. Today, Cellectis is the world leader in applying the technology of Meganuclease Recombination Systems to in vivo genome engineering and genome surgery. The company is focused on the research and development of custom-made Meganucleases for in vivo DNA interventions and also provides new tools for rational reverse genetics and targeted recombination. Cellectis develops Meganucleases that can induce unique site-directed double-strand breaks in a living cell, and can be used for biotechnological and therapeutical applications. The company is focusing on bringing "genome surgery" to clinic as a genuine new molecular medicine approach. As of today, Cellectis has entered into more than 35 deals on its Genome Engineering technologies, including with major pharmaceutical and agroscience companies. Cellectis' team today comprises 35 people including 14 PhDs and the total invested capital since the company's inception is approximately EUR 20 million.

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