Press Release

Cellectis SA reports the Engineering of large numbers of Novel Highly Specific Homing Endonucleases, in the Journal of Molecular Biology

Romainville, France - November the 21^st, 2005 - Cellectis SA, a biotechnology company specialized in rational genome engineering, announced today the report, in Journal of Molecular Biology, of the engineering of a large numbers of highly specific homing endonucleases that induce recombination on novel DNA targets.

This article describes a semi-rational approach to obtain novel highly specific meganucleases. Identification and characterization of the novel proteins was conducted on Cellectis' High Throughput Screening platform. In another report published in Nucleic Acid Research, Cellectis also describes an alternative method to select for such novel meganucleases.

Meganuclease-induced gene targeting has emerged as the universal method for efficient and precise genome engineering. Cellectis is the world specialist in Meganuclease Recombination Systems (MRS) technologies and factors influencing meganuclease-induced recombination (see recent publication in Biotechniques Vol 39 of July 2005). In nature, meganucleases are essentially represented by homing endonucleases, that trigger the spreading of genetic mobile elements through targeted homologous recombination. The structures of several of these proteins are known. This allows for site-directed mutagenesis of residues essential for DNA binding. Hundreds of novel proteins were derived from I-CreI, a homing endonuclease from the LAGLIDADG family. These novel endonucleases display a wide range of cleavage patterns in yeast and mammalian cells that, in most cases, are highly specific and distinct from I-CreI. Rules for protein/DNA interaction can be inferred from statistical analysis. Importantly, novel endonucleases could be combined to create heterodimeric protein species, thereby greatly enhancing the number of potential targets. These results describe a straightforward approach for engineering novel endonucleases with tailored DNA sequence specificities, while preserving the levels of activity and specificity of natural homing endonucleases, and thereby delivering new tools for genome engineering.

The printed version of the article will be published by the end of 2005, in Journal of Molecular Biology, but can already be accessed on line via the Journal of Molecular Biology website at: www.sciencedirect.com.

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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