Roots of Genome Engineering
Cellectis’ activities are based on genome engineering, an in vivo method for modifying an organism’s genetic data. The recent sequencing of a number of genomes – including the human genome –, of a number of viral or bacterial human pathogens, and of crop strains, has provided access to a previously unparalleled level of information. The field of functional genomics has experienced major growth, and even though a large part of the information obtained is not yet understood, it is in the process of being deciphered. Today, this considerable progress has created a genuine need for effective tools for the programming of genetic material and chromosomes.
Traditional methods of genome engineering (random insertion of foreign DNA) have been widely used by academic laboratories for fundamental research, by private institutions for improving crop strains, and in the clinical field for gene therapy. However, traditional methods presented a certain number of limitations, in technical terms but also in political and ethical terms. It has led to recombinant therapeutic proteins, first generation of GM crops and first gene therapy trials.
Cellectis offers tools for genome engineering which are rational, effective, precise and safe. These technologies eliminate the main disadvantages of most of the current genome engineering tools, randomness.
Most of the genome engineering methods currently in use are based on the random insertion of transgenes or targeted insertion at a precise site, the latter method using a recombinase and its recognition site (the Cre/lox system is an example). In both cases, this leads to the addition of a new sequence in the genome, sometimes accompanied by a number of unwanted effects. The expression of a gene depends on its chromosomal localization, and, most often, this expression depends on the tissue where the gene is expressed and evolves during the cell cycle and the development of the organism. Random insertion can therefore be seen as a relatively imprecise solution that can modify the expression of endogenous genes. It can occur in the gene or in the sequences that control gene expression.
Precision is of utmost importance in medicine. Traditional gene therapy using methods for the random insertion of transgenes nonetheless represents a step towards the medicine of the future. Even though such an approach carries major risks, its use is justified by the absence of alternative treatments for diseases which are invariably fatal. However, several problems recently encountered in gene therapy trials clearly highlight the need for a new method and cleaner technology.
In the agricultural biotechnology sector, genome engineering is experiencing an entirely different problem.
The true environmental consequences of launching GM crops on a large scale in open fields have been extensively assessed. However, the expectations of citizens, the media and governments in a number of countries have already led to a raft of strict regulations. Given the time required for the development of crop varieties, all international companies are currently trying to anticipate the growing demand for more controlled engineering methods and a limited use of foreign DNA.
Cellectis offers tools that guarantee efficacy, precision and safety in genome engineering. Cellectis’ flagship technology based on induced homologous recombination, MRS technology (Meganuclease Recombination Systems), represents a highly beneficial solution for genome modification. By modifying a given locus in the chromosome, MRS technology is a rational solution which enables the correction, replacement, targeted rewriting or precise deletion of portions of genetic material.
