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Frequently Asked Questions

What is Homologous Recombination?

Homologous recombination is a natural DNA sequence exchange mechanism, which can take place in any living cell. The mechanism is based on recognition and exchange between two similar nucleotide sequences. Once the homologous sequences are paired, a strand exchange takes place between the two molecules: this event is homologous recombination. This principle has been demonstrated and reproduced extensively in a wide variety of organisms (yet its success varies with the species to which it is applied). Nonetheless, today, homologous recombination is the leading technology in rational genome engineering (≥'activation10 000 publications to date). Many fundamental discoveries in biology have taken place with the help of homologous recombination.
Homologous recombination is a method of making site directed insertions, deletions or replacements of DNA in a living organism.

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Is Homologous Recombination patented?

Use of Homologous Recombination to target a sequence in a living cell is a CELLECTIS patented technology.

What is MRS© ?

MRS stands for Meganuclease Recombination Systems©, a CELLECTIS patented technology. MRS© uses the natural DNA maintenance mechanisms present in all living cells, making homologous recombination efficient in some difficult species such as plants or fish, and rendering it very efficient in a number of species such as mammals. This technology is based on DNA scissors, the Meganucleases, which recognize and cut specifically a unique DNA target site within a living cell.

What is a Meganuclease?

A Meganuclease is an endonuclease, a protein that binds and cuts DNA at specific target sites. Meganucleases function similarly to restriction endonucleases with the exception that their recognition sites are much larger (≥18 bp). This means that Meganucleases are very rare DNA cutters. For an 18 bp recognition site, the frequency is one out of 34 billion base pairs.

What is the enhancement of Homologous Recombination by Meganuleases? Meganuclease induced double-strand breaks have been shown to enhance recombination 1,000 – 10,000 fold compared to spontaneous homologous recombination.

What is Genome Engineering?

Genome engineering refers to all the different methods used to induce a change in the genetic program of a living cell and/or a living organism.
Genome engineering is to biologists what software programming is to computer scientists. All living organisms have a genetic program encoded in their DNA. When a mistake slips into this program, it results in a malfunction for the living organism, just like a " bug " in computer software. Changing the DNA in order to correct an error or modify the information it encodes is genome engineering.

Genome engineering uses a biological approach to treat the genetic causes of cellular malfunction. Its mode of action is rapid and brief, like surgery on DNA, and its effects are long lasting.

How does Genome Engineering work?

A number of methods can be used to modify the genetic program in living cells. They fall into two classes:
* Transgenesis by random integration of foreign DNA into the genome, using artificial chromosomes or even episomal recombinant viruses. These methods lack precision. They place resident genetic addenda into the cell. These are genetic add-ons placed outside the DNA sequence causing the malfunction. The "bug" remains in the program even with the added material. They attempt to keep long term resident foreign DNA in the cell and try to mimic natural expression patterns observed for that DNA.
* Methods allowing site directed rational modification of cellular genomes. These precise DNA surgery techniques are designed to rewrite chromosomes precisely where they should be modified. These methods correct chromosomal defects without relying on resident foreign DNA or artificial regulation. These are the cutting-edge approaches developed by CELLECTIS.

What is Genome Engineering for?

Genome engineering is one of the key activities of what is now called the "post-genomic era" (i.e. now that the genomes of a lot of different species have been sequenced, especially Human).
Very precise knowledge of the DNA sequence is required to perform DNA interventions on the genetic program. These interventions focus on two major goals:

1. Therapy:

  • Curing diseases caused by genetic defects (hereditary diseases, cancer, etc.).
  • Curing cells of viruses and parasites.

2. Rational genetics in species:

  • Improving natural living resources by rational intervention on their genetic code (animal and plant health)

With the recent completion of the human genome sequence and the systematic quest for new polymorphisms, rational genome engineering has evolved into a genuine industry.

What is the business of Genome Engineering?

Our custommers use rational genome engineering for:

  • Protein manufacturing (antibodies, biologicals)
  • Bioprocessing (antibiotics, small molecules),
  • Animal models (mice, zebrafish, worms…),
  • Pharmacogenomics (in vivo SNP screening),
  • Agricultural plants (trait improvement),
  • Food processing (enzyme production and improved microorganisms),
  • Strain improvement and metabolic engineering.

Is Cellectis a service provider?

No.
Cellectis is not a service provider. It is the first company to apply the Meganuclease Recombination System approach to in vivo genome engineering. The company is developing Meganucleases that can target a unique DNA break in vivo, as a fundamentally enabling technology for commercial applications in human therapeutics, pharmaceutical discovery, agriculture and industrial biotechnology.
Cellectis' main business is the development of novel therapeutics.
As of today, Cellectis' business efforts are to promote its technologies in all other fields where they are applicable. While Cellectis focuses internally on all human applications, the use of MRS© in animals, plants or other species is pursued through partnerships with selected companies. Working with Cellectis allows a privileged access to technologies developed by its integrated rational genome engineering platform.

Is Cellectis selling natural Meganucleases and reagents?

No.
I-SceI Meganuclease can be bought at Fermentas.
Fermentas: http://www.fermentas.com

CELLECTIS SA
RATIONAL GENOME ENGINEERING

Parc Biocitech 102 avenue Gaston Roussel - F-93235 Romainville Cedex
Tel.: +33 1 41 83 99 00 - Fax: +33 1 41 83 99 03
Last Update 03/07/2008 Legal Notice
Version Française