Press Release

Cellectis announces the publication of a paper entitled "The C-terminal loop of the homing endonuclease I-CreI is essential for site recognition, DNA binding and cleavage" in the journal Nucleic Acids Research.

Romainville, France - May the 10^th, 2007 - Cellectis SA, the rational genome engineering company specializing in the production of meganuclease recombination systems and in meganuclease engineering, today announced the publication of a new paper in the high profile journal Nucleic Acids Research (Prieto et al.,) "The C-terminal loop of the homing endonuclease I-CreI is essential for site recognition, DNA binding and cleavage". Nucleic Acids Research, 2007, 1-10 doi:10.1093/nar/gkm183 Apr 22 2007 (http://nar.oxfordjournals.org/) as a result of its collaborative research effort with the NMR and Macromolecular Crystallography Groups at the Centro Nacional de Investigationes Oncologicas (CNIO), a world-class research institute located in Madrid (Spain).

Over the last decade, meganucleases have emerged as powerful tools for efficient and precise genome engineering. This technology is a world standard in gene targeting and is used to precisely substitute, delete, add or correct genetic sequences at a chosen location in any given genome. Meganuclease Recombination Systems address a wide range of applications spanning the fields of agricultural biotechnology, protein production and genomic research tools. However, meganucleases also provide new hope for novel therapeutic agents for curing monogenic inherited diseases and viral infections. The meganuclease technology as such and some of the principle of the uses of homologous recombination were discovered at the Institut Pasteur, which then granted Cellectis worldwide exclusive rights in 2000.

Since then, Cellectis has expanded the potential of this technology by developing meganucleases with tailored specificities which are thus able to target selected genes in any given organism. This achievement was the result of a sustained long-term R&D effort with the development of a dedicated high-throughput screening (HTS) platform. Another key factor was the acquisition of specific knowledge of the intrinsic biochemical and biophysical properties of meganucleases, resulting either from in-house research at Cellectis or via collaboration with academic institutions such as the CNIO in Madrid.

The challenge of any genome engineering technology based on the induction of specific DNA cuts relies on two critical characteristics of the DNA cutter: its activity and its specificity (in order to avoid side effects). Hence, assessment of the quality and the safety of a DNA cutter is based on these two parameters. The discovery made by the Groups of F. Blanco and G. Montoya, from CNIO, and Cellectis in this collaborative study opens up new routes for the engineering of highly active and specific tailor-made meganucleases.

To date, the engineering of meganucleases has been based on modification of a series of positions located in the same, characteristic protein fold. In this paper, we describe the identification of an additional key region involved in DNA-protein interaction, modification of which can trigger differences in meganuclease-DNA binding patterns. This region might be a novel target in meganuclease engineering and may yield better tools. The publication of this paper in Nucleic Acids Research testifies to the success of Cellectis' strategy of backing research excellence in the field of meganucleases and targeted DNA recombination.

About Cellectis

Cellectis SA (www.cellectis.com) is a world-leading company in genome engineering and genome surgery. The company is focused on developing and producing custom meganucleases for in vivo DNA surgery and also provides new tools for rational reverse genetics and targeted recombination. Cellectis' products induce unique, site-directed, double-strand DNA breaks in a living cell and can be used in a wide range of biotechnological and therapeutic applications. To date, Cellectis has entered into more than 45 deals on its genome engineering technologies with major players in the pharma, biotech and agrobiotech industries. Cellectis is listed on the Euronext Alternext market (ticker code: ALCLS). For more information on Cellectis, visit our web site: www.cellectis.com

About Cellectis' technology

A meganuclease is a molecule (protein) that cuts DNA at a highly precise site on a chromosome. Once DNA is broken, it has to be repaired by the cell's natural endogenous maintenance systems. By providing a specifically engineered DNA molecule (called a repair matrix) which will be used as a template to repair the break, one can channel the repair pathway into an insertion, deletion or correction process. Thus, meganucleases can be used to trigger precise modification of specific genes in a variety of cells and organisms. By combining the meganuclease's capacity to cut DNA and DNA's ability to undergo repair, Cellectis is creating new generations of products for a wide spectrum of applications.

• Human health
  Many genetic diseases result from a single mutation in a specific gene. Meganucleases can specifically target this same gene. In parallel, a DNA repair matrix (prepared by Cellectis and including a non-mutated copy of this gene) will be introduced into the cell. Upon cleavage by the meganuclease, the repair matrix will be used as a template to restore a correct gene. By erasing the mutation, gene correction addresses the very cause of the disease, rather than its consequences
• Agrobiotech
  The process described above in human health can also be applied to plants, with the objective of replacing one gene by another, modifying a gene or shutting a gene down. The applications developed by multinational firms (such as Bayer BioSciences and DuPont-Pioneer) using Cellectis' technology are essentially aimed at improving agronomic features of crops.
• Biomanufacturing
  Biomanufacturing is a multibillion market with an annual growth rate of over 15%. It consists in the production of therapeutic proteins and antibodies using bacteria, yeasts or mammalian cells (mainly mouse, hamster and human cells). Cellectis has developed meganucleases that cut the DNA of the principal production cell lines used in biomanufacturing, thus enabling end users (contract manufacturing organizations or biopharmaceutical companies) to shorten their cell line engineering processes, stabilize production yields (and thus the quality of the final product) and improve final product features.

About Cellectis' R&D and publication policy

To deliver efficient genome engineering tools, Cellectis has focused its R&D activity on two major axes. First, Cellectis develops custom meganucleases with tailored specificity, capable of cleaving an a priori selected gene. This protein engineering process is based on the latest HTS methods, Cellectis' in-depth knowledge of the meganucleases' properties (how they bind and cleave DNA, their intrinsic plasticity, etc.) and our ability to potentially modify these properties. The second axis corresponds to optimization of the repair process, which largely depends on the design of the repair matrix.

Cellectis' policy is to foster research excellence in order to offer new solutions for genome engineering. To date, the major outcome of this effort has been the production of custom meganucleases that cleave genes of interest; this capability vastly expands the range of potential applications and is a prerequisite for therapeutic use. While the core activity (i.e. the protein engineering itself) is usually conducted solely by Cellectis, upstream studies are often performed in collaboration with major players in the field.

This effort has resulted in a growing body of know-how, of which part has been disclosed (after IP protection) in peer-reviewed journals in order to disseminate the company's achievements to a broad scientific audience. The publications listed below testify to Cellectis' technical progress and its recognition by the scientific community.

• Paques F & Duchateau P (2007). Meganucleases and DNA double-strand break-induced recombination: perspectives for gene therapy. Curr Gene Ther. 7:49-66 (Review).
• Smith J, et al. (2006). A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences. Nucleic Acids Res 34: e149.
• Gouble A et al. (2006) Efficient in toto targeted recombination in mouse liver by meganuclease-induced double-strand break. J Gene Med. 8: 616-622.
• Arnould S et al. (2006) Engineering of large numbers of highly specific homing endonucleases that induce recombination on novel DNA targets. J. Mol. Biol. 355:443-58
• Chames P et al. (2005) In vivo selection of engineered homing endonucleases using double-strand break induced homologous recombination. Nucleic Acids Res. 33:e178.
• Perez C et al. (2005) Factors affecting double-strand break-induced homologous recombination in mammalian cells. Biotechniques. 39:109-15.
• Epinat JC et al. (2003) A novel engineered meganuclease induces homologous recombination in yeast and mammalian cells. Nucleic Acids Res. 31:2952-62.

Cellectis' Forward-Looking Statements

This communication expressly or implicitly contains certain forward-looking statements concerning Cellectis SA and its business. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of Cellectis SA to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Cellectis SA is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise.

For a discussion of risks and uncertainties which could cause actual results, financial condition, performance or achievements of Cellectis SA to differ from those contained in the forward-looking statements please refer to the Risk Factors (Facteurs de Risque) section of the prospectus approved by the French Autorité des Marchés Financiers ("AMF") on January 22^nd, 2007 under visa number 07-023, available on the websites of the AMF (http://www.amf-france.org) and Cellectis (http://www.cellectis.com).

Disclaimer

This press release, and the information contained herein, does not constitute an offer to sell or a solicitation of an offer to buy or subscribe for shares in Cellectis in any country.