Engineered Meganucleases

Meganucleases are a particular class of “DNA scissors” with a high degree of specificity; they are capable of cutting a chromosome at a specific site in a living cell. In nature, meganucleases come from single-celled organisms, bacteria, yeast, algae and some plant organelles.

Natural meganucleases are active in all the organisms tested to date: they perform “cut-and-paste”-type changes in the genetic program at the site where their target sequence (very specific motif of 12-30 base pairs) has previously been inserted in the genomic DNA.

Cellectis has acquired unique expertise in the fields of meganucleases and homologous recombination, enabling it to develop comprehensive MRS technologies (Meganuclease Recombination Systems). These technologies are a very effective method for performing excisions, modifications or gene replacements in almost all living organisms.

Natural meganucleases’ high degree of specificity, together with the very low probability of the presence of their recognition site, means that this target sequence must first be introduced at the location where the “cut-and-paste” is to take place. This first stage represents a major limitation to the more widespread use of this technology in genome reprogramming because the insertion of the target sequence is a rate-limiting step.

To overcome this limitation, Cellectis modifies the recognition capability of meganucleases in order to target natural genomic DNA sequences of particular interest. These newly developed enzymes are designed according to meganucleases that exist in nature; Cellectis uses them to target well-defined DNA sequences for a given application. Cellectis has developed a high-throughput screening platform for meganucleases to create a vast collection of “DNA scissors” and associate them with modified-specificity MRS technologies. This development unleashes the full potential of the technology developed by Cellectis.

MRS technology is a major breakthrough in genome engineering and genome surgery and paves the way for further developments in the future.