Custom Meganucleases

Cutting a chromosome at a specific place in living cells can be achieved by meganucleases, a particular class of DNA scissors with very high specificity. In nature, meganucleases come from unicellular organisms, bacteria, yeasts, alga and some plant organelles. Natural meganucleases operate in all organisms tested so far, and are used to make "cut and past" changes in the genetic program at the site where their target sequence (very specific combinations of 12 to 30 base pairs) has been previously inserted into the genomic DNA. Cellectis has developed a unique expertise in combining meganucleases with specially engineered targeting DNA matrices into complete Meganuclease Recombination Systems (MRS^©), used for very efficient gene excision, gene correction or gene replacement, in virtually any organism.

The high level of specificity of a natural Meganuclease has always implied a preliminary insertion of the natural target sequence at the location where the "cut and past" will occur. This first step has been seen as a strong limitation for a wider use of the technology in genome reprogramming.

To overcome this limitation, Cellectis engineers meganucleases in order to customise their recognition of natural genomic DNA target sequences of particular interest. These newly designed enzymes are evolved from meganucleases found in nature and used as backbones that Cellectis reengineers to target appropriately chosen DNA sequences for a given application. Cellectis has developed a meganuclease high throughput screening platform to produce a large collection of new cutters and combine them into custom MRS^© (c-MRS). This development unleashes the full potential of Cellectis' technology.
c-MRS is a major genome engineering technological breakthrough in genome engineering and Genome Surgery and provide new hope for the future.