Cellectis Publishes Manuscript in Frontiers Bioengineering and Biotechnology Unveiling Efficient Multitool Multiplex Gene Engineering combining TALEN and TALE Base Editors

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, today published a manuscript in Frontiers Bioengineering and Biotechnology demonstrating the feasibility of efficient multiplex gene engineering using a combination of two different molecular tools: Cellectis' TALEN gene editing technology (TALE nuclease) and a TALE-BE (TALE Base editor).

TALE base editors are a recent and very important addition to the gene editing landscape. This approach does not create DNA double strand breaks 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.

Cellectis used a screening approach to gain in-depth insights into the editing rules driving TALE-BE activity and applied this knowledge to design highly efficient TALE-BE compatible with potential therapeutic application. Moreover, TALE-BE show insignificant levels of by-products such as indels.

Cellectis scientists combined two molecular tools, a TALEN and a TALE-BE, to perform a double gene Knock Out (KO) of TRAC and CD52, a combination of target genes used for allogeneic CAR T-cell adoptive therapies. This combination of molecular tools paves the way to simultaneous multiplex gene engineering with more controllable outcomes.

A multiplex/multitool strategy presents several advantages: firstly, it prevents the creation of translocations often observed with the simultaneous use of several nucleases. Secondly, it allows for the possibility of going beyond multiple knock-outs while still allowing gene knock-in at the nuclease target site, altogether extending the scope of possible application,' said Alex Juillerat, Ph.D., Vice President Gene Editing & New York Lab Head at Cellectis. 'The precise positional rules we have determined for TALE-BE will allow Cellectis to unleash the full potential of these technologies for future applications.'

Designed TALE-BE targeting CD52 achieved very high frequency of gene knock-out (up to 80% of phenotypic CD52 knock out).

When TALE-BE was combined with a TALEN targeting the TRAC locus, very high frequency of double gene knock-out (up to 75% of phenotypic double gene knock-out) was achieved without the creation of translocations between the two targeted loci.

This article is available on Frontiers in Bioengineering and Biotechnology website by clicking on this link.

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