Cellectis’ Novel Gene Editing Tech Could Unlock Scalable Cell Therapies

NEW YORK, NY – November 19, 2025

A Shift Away From Viruses

Cellectis, a clinical-stage biotechnology company, is making waves with the publication of research detailing a novel, non-viral gene editing process. The company’s innovative approach, utilizing circular single-stranded DNA (CssDNA), has demonstrated significantly improved efficiency in gene insertion into hematopoietic stem and progenitor cells (HSPCs) – a crucial step toward creating readily available, “off-the-shelf” cell and gene therapies. This advancement addresses a long-standing challenge in the field: developing safe and efficient methods for delivering genetic material without relying on viral vectors, which can trigger immune responses and present manufacturing complexities.

The current landscape of gene therapy is heavily reliant on viral vectors, particularly adeno-associated viruses (AAVs). While effective, these vectors are expensive to produce, can elicit immune responses, and have limited packaging capacity. The push for non-viral alternatives has been ongoing, but many methods have struggled with low efficiency and transient gene expression. Cellectis’ CssDNA technology appears to overcome these hurdles, offering a compelling path toward more scalable and affordable therapies.

The Science Behind CssDNA

Published in Nature Communications, Cellectis’ research demonstrates that CssDNA achieved a 3-5x higher gene insertion efficiency—exceeding 40%—compared to traditional linear single-stranded DNA in HSPCs. The technology’s compatibility with various gene editing tools, including TALENs, further expands its versatility. “The key innovation here isn’t just avoiding the virus, but achieving consistent, high-level gene insertion in these critical stem cells,” explains one expert familiar with the research. “That’s what makes this technology particularly exciting.”

CssDNA’s circular structure is believed to enhance its stability and protect it from degradation within cells. It also appears to facilitate more efficient access to the cell's genome. While the initial research focuses on HSPCs, the technology is also applicable to other cell types, including T cells, broadening its potential therapeutic applications. Cellectis has already filed patent applications covering the CssDNA technology, including methods of production and use for gene editing, indicating a strong commitment to protecting its intellectual property.

Implications for Cellectis and the Broader Market

For Cellectis, CssDNA represents a strategic investment that could significantly enhance its position in the rapidly evolving gene therapy market. The company's current pipeline is heavily focused on allogeneic CAR T-cell immunotherapies— “off-the-shelf” cancer treatments derived from donor cells. While CAR T-cell therapy is showing promise, the manufacturing process is complex and expensive. Integrating CssDNA into their CAR T-cell manufacturing process could potentially lower costs and improve scalability.

“They’ve staked a lot on allogeneic CAR T-cells,” notes a financial analyst following the biotech sector. “This CssDNA technology isn't necessarily a pivot away from that strategy, but it’s a potential enabler – a way to make their existing pipeline more efficient and competitive.”

Beyond CAR T-cells, the CssDNA technology could also open doors for Cellectis to expand into new therapeutic areas, such as genetic blood disorders like sickle cell disease and thalassemia. These conditions require stable gene insertion in HSPCs, making CssDNA a potentially ideal delivery method. The company’s financial reports indicate a cash runway extending into the second quarter of 2025, but further investment or partnerships will likely be needed to fully realize the potential of CssDNA and advance its pipeline.

The Race for Non-Viral Delivery

Cellectis isn’t alone in its pursuit of non-viral gene editing solutions. Numerous companies and academic labs are exploring alternative delivery methods, including lipid nanoparticles (LNPs), electroporation, and polymeric nanoparticles. LNPs have gained prominence with mRNA vaccines, but achieving stable gene insertion remains a challenge. Electroporation is efficient ex vivo but not suitable for in vivo applications.

“The field is hungry for a truly versatile and efficient non-viral delivery method,” says a gene therapy researcher at a leading academic institution. “There are a lot of promising approaches, but CssDNA stands out because of the reported efficiency and stability. The ability to achieve high-level gene insertion without a virus is a significant step forward.”

The success of CssDNA will ultimately depend on further validation in preclinical and clinical studies. Long-term safety and efficacy data will be crucial to demonstrate its potential as a viable alternative to viral vectors. However, the initial research suggests that Cellectis has made a significant breakthrough, paving the way for a new generation of safer, more scalable, and more accessible cell and gene therapies. The company is now focused on optimizing the CssDNA technology and integrating it into its manufacturing processes, with the goal of bringing these innovative therapies to patients in need.