Moligo Technologies and Cellectis Demonstrate Potential of Enzymatic Single-Stranded DNA for Non-Viral Gene Editing in Nature Communications

Nature Communications article shows highly efficient and scalable gene insertion of long, single-stranded DNA donor templates in hematopoietic stem cells

STOCKHOLM, Nov. 21, 2025 /PRNewswire/ -- Moligo Technologies, a DNA synthesis company advancing gene therapies, announced today the publication of an article in Nature Communications that demonstrates enzymatically synthesized single-stranded DNA (ssDNA) as a highly efficient non-viral donor template for gene insertion in hematopoietic stem and progenitor cells (HSPCs). The study, co-authored by Moligo and Cellectis, a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, further validates long, ssDNA as an optimal method for non-viral gene therapy that could pave the way for the next generation cell and gene therapies.

"This study provides clear evidence that Moligo's enzymatically produced long ssDNA vectors can serve as a robust, scalable alternative to viral delivery," said Moligo CEO Cosimo Ducani, Ph.D. "Importantly, it demonstrates the strength of our cell-free synthesis platform and its expanding role in non-viral cell and gene engineering. We're proud to reach this milestone, which reinforces our commitment to developing next-generation DNA tools that enable safer, more effective, and more accessible cell and gene therapies worldwide. This collaboration also serves as a powerful testament to the value of strategic partnerships in accelerating innovation."

Viral vectors are currently the gold standard for gene insertion in several cell types, including HSPCs, but they raise concerns related to safety, efficacy, and affordability. In recent years, non-viral DNA template delivery has been combined with engineered nucleases to introduce ssDNA donors. Although effective, this strategy was limited to short DNA templates and therefore mainly supported gene correction. Attempts to use longer double-stranded DNA vectors for gene insertion have been hindered by their cytotoxicity and immunogenicity, further constraining the range of feasible applications.

Moligo harnessed the enzymatic DNA synthesis of long ssDNA, both linear and circular, which have been adopted by Cellectis to develop a robust gene insertion process.

These results demonstrate:

• Moligo's ssDNA vectors can be used for high knock-in efficiency in HSPCs, and that the circular ssDNA format, in this case, is 3-5 times more efficient than the linear one.
• Moligo's ssDNA vectors 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 have also shown that HSPCs edited with circular ssDNA exhibit a greater capacity to engraft and retain their gene edits in murine models than those edited using AAV6.

"These results establish the CssDNA (circular single-stranded DNA) and TALEN® editing 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.

ABOUT MOLIGO

Moligo Technologies produces long, ultra-pure, complex DNA at industrial scale using a proprietary enzymatic synthesis process to overcome the challenges of chemical methods. The company's innovative PCR-free "injection-molding" platform can be scaled to produce kilograms of DNA, enough material to enable any cell- or gene-based therapy to go from the lab through clinical trials. With a specialty in complex, ultrapure single-stranded DNA 100 percent sequence verified and more than 10,000 bases long - and at scalable volume - Moligo helps companies take safer, more effective gene-based therapeutics, vaccines, and diagnostics over the finish line and to the patient. Moligo was founded in 2019 and is privately held.

About Cellectis    

Cellectis is a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies. The company utilizes an allogeneic approach for CAR T immunotherapies in oncology, pioneering the concept of off-the-shelf and ready to use gene-edited CAR T-cells to treat cancer patients, and a platform to develop gene therapies in other therapeutic indications. With its in-house manufacturing capabilities, Cellectis is one of the few end-to-end gene editing companies that controls the cell and gene therapy value chain from start to finish.    

Cellectis' headquarters are in Paris, France, with locations in New York and Raleigh, NC. Cellectis is listed on the Nasdaq Global Market (ticker: CLLS) and on Euronext Growth (ticker: ALCLS). To find out more, visit www.cellectis.com and follow Cellectis on LinkedIn and X. 

SOURCE Moligo Technologies