By James Etheridge

BioWorld International Correspondent

PARIS ¿ Cellectis SA, a French start-up that describes itself as a ¿rational genome engineering¿ company, signed a technology licensing agreement with the German company Zentaris AG giving the latter exclusive worldwide rights to its sLTR (single Long Terminal Repeats) gene transfer technology for application in cancer therapies.

Cellectis¿ sLTR vectors are designed to make it possible to eliminate tumor cells without affecting healthy tissues, since they enable a gene to be introduced into cellular DNA, after which both the vector and the transferred gene self-destruct. Using this technology, MainGen Biotechnology, a subsidiary of Frankfurt-based Zentaris, will develop ¿self-deleting suicide vectors¿ (SDSVs) for selectively eliminating the targeted tumor cells.

About half of human cancers are characterized by a deficiency in the synthesis of the p53 protein, and MainGen plans to load suicide genes onto an SDSV and introduce them into cells bearing this deficiency, because once in situ the genes are expressed and result in cell death. The advantage of Cellectis¿ technology is that it can limit the action of suicide genes to tumors. In healthy tissues expressing p53 normally, the vector self-deletes from cellular DNA and eliminates itself altogether with the suicide gene, leaving the cell untouched.

Zentaris will apply this technology to the treatment of various cancers, including colorectal, brain and throat cancers. In the view of Cellectis, sLTR technology is particularly suited to gene therapies for cancer.

Paris-based Cellectis was founded early in 2000 and is a spin-off from the Institut Pasteur, a nonprofit medical research establishment. General Manager David Sourdive told BioWorld International that the company was founded by nine researchers, not all of them from Pasteur, and remains housed in the Pasteur Institute¿s biotechnology business incubator, BioTop, although it already has a work force of 29.

The company¿s seed capital was provided by its founders, which together hold 75 percent of its equity, while the Pasteur Institute owns the other 25 percent. Sourdive said it is engaged in an initial funding round, which he expects to be completed by the year-end, but he declined to give a ballpark figure for the amount being sought.

All of Cellectis¿ core technology was provided by Pasteur, which has granted it full rights to nine families of patents. They comprise a set of tools making it possible to rewrite the genome, or perform safe ¿genome surgery,¿ as Sourdive put it. He added that, while the need for precision genome engineering is now recognized, Cellectis has the field to itself as far as he knows.

Cellectis¿ technology platform is composed of several strands, including homologous recombination, meganucleases, and applications of DRAM (D-loop recombination activated by meganucleases). Among other things, it is developing new types of meganucleases that each has a given recognition and restriction site and a characterized enzymatic activity, and has been optimized for in vivo expression and activity. Some are custom-made meganucleases for specific clients that yield enzymes for specific uses. These enzymes are designed to cleave DNA sequences for the purposes of precision genome engineering.

Using these tools, Cellectis can modify the genome in living organisms by MRS (meganuclease recombination system), which uses the natural DNA maintenance mechanisms present in all living cells that repair damage to genomic DNA. MRS makes homologous recombination possible in plants and fish and renders it very efficient in mammals, since it is based on the construction of synthetic meganucleases that recognize selected DNA motifs. These enzymes thus cut their target without damaging the remainder of the genome. Another important application is in the engineering of strains for recombinant protein production.

In addition, Cellectis offers a full range of DRAM-based products for in vivo linearization of DNA introduced into cells to optimize activity and limit degradation by cellular exonucleases.

The company intends to use its genome engineering technology to develop drugs for treating single-gene diseases, such as cystic fibrosis, Duchenne¿s disease and familial hypercholesterolemia, as well as viral infections. However, it is at the very early stages of preclinical development. In the meantime, Cellectis will generate some income by concluding more technology licensing agreements.