Meganuclease platform technologies

Cellectis’ Meganuclease Platform is a Product Platform

The Meganuclease Platform is an automated platform set to generate customized Meganucleases in order to induce site-directed recombination at chosen natural loci in living cells. The platform performs high throughput screening of variant meganucleases rationally designed by Cellectis' R&D team to induce recombination at specific DNA targets in cells. Each newly produced Meganuclease is tested for activity through a standard routine cell-based assays developed at Cellectis. The platform generates products that are Meganuclease Recombination Systems (MRS). These MRS products are dedicated to rational genome engineering for a variety of DNA targets and organisms.

Cell-based-assays are done by the automated high throughput platform

Meganucleases makes no cleavage without tight recognition

Meganucleases bind and cut DNA targets of 18 to 24 base pairs, hence, the complexity of combinations range from 70 billions to 20 trillions. Meganucleases structure shows that DNA cutting activity is just within the middle of the DNA recognition domains. It's this original feature that makes meganuclease cuts highly specific and totally linked to the perfect recognition of the large DNA target to be cleaved. That's why meganucleases are so specific and can be used as the ultimate "genome surgery" tools in living cells and organisms.

Meganucleases are plastic proteins

Meganuclease fit onto DNA in the same way a key would fit a lock. The DNA target motif is specifically recognized by a set of amino acids pointing toward the DNA target and fitting perfectly into the DNA motif. If the meganuclease's set of amino acids does not fit into the DNA target, the cleavage won't happen (no blue spot). Cellectis design and engineer changes of such amino acids of Meganucleases to fit designated DNA targets. Through a structural-based protein design, Cellectis generates large collections of variant Meganucleases with different specific protein/DNA interactions. The screening of Meganuclease-induced recombination events at a given DNA target is performed through cell-based assays and displayed on arrays that are automatically analyzed. Results are stored in the Cellectis' OmegaBase'. Resulting products are integrated into an MRS and used for any genome surgery or genome engineering purposes.

Engineered collections of meganucleases are challenged to DNA targets	Hits are spotted on arrays and characterized