TALEN®

The real power of gene editing is being able to choose exactly where to edit a gene. Editing genes allows disabling a functional gene, correcting a gene, or replacing or inserting a DNA sequence at a specific chosen location in a genome. Cellectis has 25 years of expertise and knowledge in nucleases and gene editing, with product candidates of the highest quality, precision, and efficacy. At Cellectis, we design nucleases that cut a specific “gene of interest” in the genome. Cellectis is leading the development and implementation of TAL nucleases.

TAL nucleases, or TALEN®

TALEN® is based on a class of proteins derived from transcription activator-like effectors, or TALEs. TALEs are highly specific DNA-binding proteins that feature an array of 33 or 34-amino acid repeats. Each repeat is highly conserved, with the exception of the so-called repeat variable di-residues (RVDs) at amino acid positions 12 and 13. The RVDs determine the DNA sequence to which the TALE will bind. This simple one-to-one correspondence between the TALE repeats and the corresponding DNA sequence makes the process of assembling repeat arrays to recognize novel DNA sequences straightforward. These TALEs can be fused to the catalytic domain from a DNA nuclease, FokI, to generate a transcription activator-like effector nuclease (TALEN®). The resulting TALEN® constructs combine high specificity and activity, effectively generating engineered sequence-specific nucleases that bind and cleave DNA sequences only at pre-selected sites.

TALEN® products are designed by fusing the DNA cutting domain of a nuclease to TALE domains, which can be tailored to specifically recognize a unique DNA sequence. These fusion proteins serve as readily targetable “DNA scissors” for gene editing applications that enable us to perform targeted genome modifications such as sequence insertion, deletion, repair and replacement in living cells.

The main advantage of TALEN® is their target recognition system based on a simple, easy-to-predict code. TAL nucleases are extremely precise, specific to their target and efficacious, due in part to the length of their 30+ base pairs binding site. They have many applications in genome engineering and their specificity makes them the world's best technology for therapeutic applications. Cellectis uses TALEN® for its therapeutic applications. TALEN® are the most precise (genomic targeting with TALEN® can be performed within a 6 base pairs range of any chosen single nucleotide in the entire genome), specific (recognition site is of 30+ base pairs long), and efficacious (for example, TCR-α can be knocked-out with over 85% efficacy in T-cells in routine) tool of gene editing. In addition, vectorization of TALEN® is simple and easy.

TALEN® is a registered trademark owned by the Cellectis Group.

Our approach aims to deliver an off-the-shelf product with the following benefits:

• Broad availability. Enable products to be shipped globally, thereby reducing deployment obstacles and providing accessibility to a broad patients population;
• Cost-effectiveness. Streamlined manufacturing process has the potential to reduce costs;
• Novel Features. Develop products with specific safety and control properties;
• Compatibility. Develop products taking into consideration the current standards of cancer care;
• Consistency. Qualify and develop cancer products that are designed for optimal dosage, while reducing batch-to-batch variability. In addition, vectorization of TALEN® is simple and easy.

Due to these factors, TALEN® constructs have many applications in gene editing and represent the best available technology for therapeutic applications.