Cellectis’ Post

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We found 3 key factors determinant for efficient TALE base editing ✂ First, what are TALE base editors? 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. They represent a promising therapeutic strategy for genetic diseases. Interesting, right? But, to broaden the scope of possible applications, we need to understand the 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. That’s why we 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. We found 3 key factors: 💡 Spacer length 💡TALEB architecture 💡Composition of surrounding bases All of them 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. Any thoughts on this? Drop them in the comments ⤵ For those interested in gene editing advancements, the full paper is available in Scientific Reports : https://lnkd.in/eSRZxyfN #GeneEditing #MolecularBiology #Genetics #BiotechResearch

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