A New Model for Studying Meganuclease-Based Therapeutic
Approaches Featured in International, Peer-Reviewed Journal Blood
Paris, October 8, 2009 – Cellectis S.A. (Alternext: ALCLS), the French genome engineering
company, announced that the results of experiments conducted by Dr. Jean-Pierre de Villartay's group
from the French National Institute for Health and Medical Research (INSERM unit U768, headed by
Professor Alain Fischer) at Necker Children's Hospital, in collaboration with researchers at Cellectis
have recently been published in the international, peer-reviewed journal Blood. The article reports the
establishment of a new line of mice that enabled detailed investigation of the adaptive immune
response ("Reduced immunoglobulin class switch recombination in the absence of Artemis", Rivera-
Munoz et al., Blood, Aug 19, 2009). This line also constitutes an important model for studying the
meganuclease-based correction of genetic diseases thus leading Cellectis’ technology further in this
therapeutic field.
The Artemis gene product is involved in the repair of DNA double-strand breaks. Mutations in this
gene exist in humans and are responsible for severe combined immunodeficiencies (SCIDs) -
conditions which are rapidly fatal and which can only be cured by hematopoietic stem cell
transplantation.
In order to develop experimental models for the human disease, the Necker and Cellectis researchers
bred lines of mice in which the Artemis gene was absent either from all the cells (in which case the
animal lacks mature lymphocytes) or only from mature B lymphocytes. The results confirmed that
Artemis is involved in the maturation of B and T lymphocytes and in several steps in the production of
immunoglobulins - the molecules responsible for the humoral, adaptive immune response.
The work will make it possible to test new approaches for treating SCIDs, especially using
meganucleases. "This model will enable us to study in vivo DNA repair in hematopoietic stem cells - a
significant