Taconic, a global provider of genetically engineered mouse and rat models and services, and Le Centre Européen de Recherche en Biologie et en Médecine – Institut de Génétique et de Biologie Moléculaire et Cellulaire (CERBM-IGBMC) announced a global cross-licensing agreement to improve access to Cre-ERT technology for inducible gene targeting in genetically engineered rodents.

Under the agreement each party will be able to generate, sell and use Cre-ERT mouse lines for tamoxifen induction experiments. Further, Taconic will play a role in helping companies acquire needed rights from CERBM-IGBMC to perform induction studies in Cre-ERT gene targeted mouse lines. Taconic and CERBM-IGBMC are the only fully licensed service providers of the Cre-ERT technology. Combining the access rights to both patent families is specifically important because it equips researchers to explore gene function in adult mice.
 
Cre-ERT technology was developed independently by scientists at two organizations: Francis Stewart at the European Molecular Biology Laboratory (EMBL) as well as Pierre Chambon and Daniel Metzger at the CERBM-IGBMC. Taconic is the exclusive commercial license holder of the EMBL patent portfolio broadly covering the use of ligand-dependent site-specific recombinases. The CERBM-IGBMC patents cover methods for performing inducible gene targeting in transgenic mice expressing a Cre-ERT fusion protein. The method employs administration of tamoxifen to transgenic mice to induce Cre-mediated recombination.
 
The agreement by Taconic and CERBM-IGBMC to further develop and provide access to Cre-ERT technology addresses key challenges relating to understanding cancer, metabolic disorders, stroke and other diseases.  “We are very pleased to partner with CERBM-IGBMC to further develop the effective application of Cre-ERT technology in genetically engineered mouse models” stated Todd Little, President of Taconic. “Cre-ERT technology is a powerful tool for studying gene function and expression in many tissues.”
 
The agreement also enhances both organizations’ efforts to bring better, more predictive mouse models to market for use by scientists worldwide. “We have greatly contributed to the development and success of the “Cre-ERT” technology, and will continue to make it freely available to the academic scientific community,” said Professor Chambon at the CERBM-IGBMC. “We are very happy with this agreement, and hope that it will contribute to the generation of several new mouse models of human diseases for use in drug discovery and development,” said Dr. Daniel Metzger at the CERBM-IGBMC.

Cre-ERT technology is based on an enzyme called Cre recombinase. This enzyme is able to recombine specific sequences of DNA called loxP. Upon encountering two separate loxP sites flanking a target nucleotide sequence, Cre recombinase deletes this intervening sequence by an irreversible recombination event between the loxP sites. By excision of a loxP flanked (floxed) critical region of a gene, the gene can be conditionally knocked out only after Cre is expressed. The spatial control of the conditional knock-out can be achieved by driving Cre activity under a tissue-specific promoter in transgenic mice. In order to generate an inducible knock-out, the Cre enzyme has been fused to a mutated ligand-binding domain of the human estrogen receptor (ERT). Upon the introduction of the synthetic estrogen receptor antagonist tamoxifen, the Cre-ERT construct enters the nucleus and induces the targeted mutation. ERT binds tamoxifen but not to endogenous estrogens, which allows Cre-ERT to remain cytoplasmic in animals that are not treated with tamoxifen. The temporal control by tamoxifen permits to study gene function at the desired time. This can help to elucidate the gene function in adults which is important for drug discovery and basic research.

The Institute of Genetics and Molecular and Cellular Biology (IGBMC) which was created in 1994 by Pierre Chambon is one of the main European centers of biomedical research that combines, within the CERBM-IGBMC, Units of the INSERM, the CNRS and the University of Strasbourg. Besides four scientific departments, the CERBM-IGBMC includes scientific services and advanced technological platforms, such as the Mouse Clinical Institute (ICS), which are also open to the external scientific community.