Cellectis A/S (NASDAQ: CLLS ) on Wednesday published 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).
HSPCs are rare, self-renewing cells in the bone marrow that mature into all blood cells, including red blood cells, white blood cells, and platelets.
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 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 applies 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 .
As of September 30, 2025, Cellectis had $225 million in consolidated cash, cash equivalents, restricted cash, and fixed-term deposits. The company believes its cash, cash equivalents, and fixed-term deposits will be sufficient to fund its operations into the second half of 2027 .
Price Action: CLLS stock is up 8.27% at $4.45 at the last check on Thursday.
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