Press Release

Cellectis S.A. announces the publication of a Journal Nucleic Acids Research (NAR) article on artificial homing endonucleases.

Romainville, France - January the 08^th, 2007 - Cellectis S.A., a biotechnology company specialized in genome engineering and developing a new range of products for the custom rewriting of DNA sequences for the research, healthcare and industrial fields, announced today the publication of a paper entitled "A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences" in the prestigious journal Nucleic Acids Research (http://nar.oxfordjournals.org/cgi/content/full/34/22/e149- Nucleic Acids Research, 2006, Vol. 34, No. 22 e149 - that publishes the results of leading edge research into physical, chemical, biochemical and biological aspects of nucleic acids and proteins involved in nucleic acid metabolism and/or interactions. This article describes the first artificial homing endonucleases whose specificity has been entirely redesigned to cleave a naturally occurring sequence.

Meganucleases, or homing endonucleases are sequence-specific endonucleases with large (>14 bp) cleavage sites that can be used to induce efficient homologous gene targeting in cultured cells and plants. These findings have opened novel perspectives for genome engineering in a wide range of fields, including gene therapy. However, the number of identified homing endonucleases does not match the diversity of genomic sequences, and the probability of finding a homing site in a chosen gene is extremely low. Therefore, the design of artificial endonucleases with chosen specificities is under intense investigation.

Previously, we have described the identification of hundreds of novel endonucleases with locally altered substrate specificity derived from I-CreI, a Chlamydomonas reinhardtii protein belonging to the LAGLIDADG family of homing endonucleases. As these mutations affect two distinct and relatively independent DNA binding sub-domains, we were able to show, in this recent paper, that mutations in different parts of the protein could be assembled to create novel endonucleases with predictable substrate specificities. We used these findings to assemble four sets of mutations into heterodimeric endonucleases cleaving a model target and ultimately a sequence from the human RAG1 gene, mutations which are associated with severe combined immune deficiency (SCID).

The making of these combinatorial mutants represents a key step towards the global engineering of the DNA binding interface of LAGLIDADG homing endonucleases and opens up significant possibilities for genome engineering and eventually gene therapy.

About Cellectis S.A.

Cellectis S.A. is a biotech company developing innovative, proprietary technologies for genome engineering: a new class of "molecular scissors" - MeganucleaseTM enzymes - capable of recognizing, binding and cutting DNA with extremely high specificity. The company is developing and commercializing Meganuclease Recombination Systems (MRSs) which combine these molecular scissors with a DNA matrix for targeting and modifying a gene of interest in vivo (and without affecting the rest of the genome) via the action of the cell's natural maintenance and repair system. By developing this first-in-class technology on the industrial scale, Cellectis has opened the way to rational genome engineering, which seeks to accurately and reliability insert, modify, modulate or correct genes in any living organism - without the addition of foreign genes, which are often imprecise and poorly tolerated. Cellectis is currently developing 8 MRSs.

Founded in 2000 by André Choulika and David Sourdive, Cellectis is a spin-off from Institut Pasteur in Paris, which has granted the company exclusive rights to a portfolio of patents. The company holds a portfolio of 27 granted patents and 69 pending applications. Since its creation, Cellectis has raised 17.5 million euros in two rounds (in 2000 and 2002) to support its R&D and commercial development. The company's principal shareholders are AGF Private Equity, BankInvest Biomedical Venture, Edmond de Rothschild Investment Partners, Kaminvest Holding and Odyssée Venture. To date, Cellectis has signed 45 collaboration agreements and alliances worldwide with pharma companies (including AstraZeneca, Merck & Co., Wyeth and Shire), agrochemical groups (including Bayer, DuPont and BASF) and biotech companies (including Genentech, Regeneron and Lexicon Genetics) worldwide. Cellectis' corporate headquarters are located on the Biocitech biopark at Romainville near Paris. It currently has 40 staff, including 16 PhDs.

For more information on Cellectis, visit our web site: www.cellectis.com

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