Genome Engineering

Cellectis is a company based on genome engineering. Genome engineering is the in vivo modification of the genetic information of an organism. The recent sequencing of many genomes, including the human genome, many human viral or bacterial pathogens, and vegetal crop strains, has provided a huge set of data. Meanwhile, functional genomics is exploding, and if most of this information is still not understood, deciphering is in process. Now, this incredible leap has created a real need for efficient tools that will allow us to get a hold on the genetic material, the chromosomes.

Genome engineering has been widely used in the past in academic laboratories, for basic research purpose, but also in private institutions, for the improvement of crop strains, and in the clinical field for gene therapy. However, the classical methods have proved to have a number of limitations, linked with technical artifacts, as well as ethical and political considerations.

Cellectis provides tools for efficient, precise, and safe genome engineering. These technologies bypass the major drawbacks of most current genome engineering technologies.

Most of the current genome engineering methods rely on the random integration of transgenes, or on targeted integrations at a chosen site, mediated by a site-specific integrase (the Cre/Lox system is an example). In both cases, the net outcome is the addition of a new sequence in the genome, with sometimes-unexpected side effects. The expression of a gene depends on its chromosomal location, and most of the time, this expression is finely tuned during the cell cycle, among different tissues, and during different phases of development. Therefore, random integration can be considered as a rather inaccurate solution. In addition random integration can be very disruptive, since the integration can occur in another gene, or in sequences governing the expression of another gene.

In the medical field, accuracy is a primordial issue. Classical gene therapy by random integration of transgenes is clearly not the ultimate medicine. Although physicians are aware of the risks of the methodology, its use can be justified by the absence of alternative treatment for a disease that invariably leads to death. Several recent problems in gene therapy trials have clearly stressed the need for an alternative, cleaner technology.

In the agrobusiness, genome engineering is facing another kind of problem. We still have no clues about the real ecological consequences of launching large scale cultures of GMOs in open field, but in many countries, the citizens, the media and the governments have largely anticipated them, establishing a tight network of regulations. This trend is very likely to spread, and given the time needed to develop new crop varieties, all the international companies are now trying to anticipate a growing demand for better controlled engineering with as little foreign DNA as possible. In the near future, it is possible that even a 50 bp stretch of foreign DNA (the size of a LoxP site) will be not acceptable.

Cellectis provides tools for precise, efficient and safe genome engineering. Cellectis’ core technologies, the Meganuclease Recombination Systems (MRS©), based on induced homologous recombination are an advantageous mean to modify the genome. By modifying a given locus in the chromosome, MRS© allow for gene correction, targeted gene rewriting and precise gene deletion in a rational way that leaves little room for artifacts.