Cellectis Publishes a Scientific Article Unveiling Three Key Factors for Efficient TALE Base Editing

New York, NY – June 20, 2024 – Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, announced today the publication of a manuscript in Scientific Reports, demonstrating how three key factors can be determinant for efficient TALE base editing.

TALE base editors are a recent and important addition to the gene editing landscape. By design, TALE base editors do not create break within DNA strands as does CRISPR/Cas9, or other engineered nucleases, and is a promising therapeutic strategy for genetic diseases. A key aspect to broaden the scope of possible applications is our comprehension of design rules.

TALE base editors rely on the deamination of cytidines within double strand DNA, leading to the formation of an uracil (U) intermediate. These molecular tools are fusions of transcription activator-like effector domains (TALE) for specific DNA sequence binding, split-DddA deaminase halves that will, upon catalytic domain reconstitution, initiate the conversion of a cytosine (C) to a thymine (T), and an uracil glycosylase inhibitor (UGI).

Previous works have pointed towards the positioning of targeted cytosine to be a key determinant for efficient editing.

To extend the understanding of key determining factors allowing efficient TALE base editing (C-to-T conversion), Cellectis investigated whether the nature (length and composition) of the linker that connects the TALE array with the split deaminase catalytic heads could impact C-to-T conversion within the editing window.

The datasets presented in this paper highlight how three key factors, spacer length, TALEB architecture and composition of the surrounding bases, can impact editing outcomes and further improve our understanding of TALE base editors' activity and specificity, leading to the possibility to tune and control editing using educated designs.

“This experimental strategy used by Cellectis to characterize editing profiles in depth and in a high throughput format could easily be applied to any new editors to continue expanding this platform for potential therapeutic applications” said Maria Feola, Scientist III, Manager, Gene Editing at Cellectis.

Research data specifically underlines the primordial importance of the positions preceding the targeted TC, which markedly increases editing efficiency. 

The article is available on Scientific Reports website by clicking on this link: https://www.nature.com/articles/s41598-024-63203-8