Cellectis Publishes Nature Communications Article on a Non-Viral Gene Editing Process Enabling Efficient Gene Insertion in Hematopoietic Stem Cells

New York, NY – November 19, 2025 – 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 publishes an article in Nature Communications establishing circular single-stranded DNA (CssDNA) as a highly efficient non-viral DNA donor template, for gene insertion in hematopoietic stem and progenitor cells (HSPCs).

Gene editing of HSPCs offers the potential for long-term therapeutic benefit. While viral vectors such as AAV6 are commonly used for gene insertion, they raise safety and efficacy concerns. Over the past decade, non-viral DNA templates delivery has emerged as promising alternatives and have been used with nucleases to target short single-stranded linear DNA corrective template in HSPCs.

Although non-viral approaches were initially limited to making only small corrections within defective genes, Cellectis harnessed its TALEN^® technology and CssDNA donor templates, to develop a robust gene insertion process. This process enables precise and efficient integration of large genetic sequences within therapeutically relevant subpopulations of HSPCs, significantly expanding the potential of non-viral gene therapy.

The results show that:

• CssDNA achieved 3-5 times higher knock-in efficiency than linear single stranded DNA (LssDNA), with values surpassing 40%.
• CssDNA can be used to insert genes at multiple loci in HSPCs and is applicable to other cell types of therapeutic interest, including primary T cells.
• Comparative studies also showed that CssDNA-edited HSPCs demonstrate a higher propensity to engraft and maintain gene edits in a murine model compared to AAV6-edited HSPCs.

“These results establish the CssDNA process as an efficient non-viral gene insertion strategy, and mark a pivotal advance towards the development of next-generation cell and gene therapies” said Julien Valton, Vice President of Gene Therapy of Cellectis.

The article is available on Nature Communications website here.