Cellectis announced significant advances in non-viral gene therapy and base editing safety at the European Society of Cell and Gene Therapy (ESGCT) annual congress in Sevilla, Spain, presenting data that could reshape approaches to gene editing in therapeutic applications.
Breakthrough in Non-Viral Gene Delivery
The clinical-stage biotechnology company presented research demonstrating the potential of circular single-stranded DNA (CssDNA) as a universal template for gene therapy. Julien Valton, Ph.D., Vice President Gene Therapy at Cellectis, presented findings showing that CssDNA editing achieved high gene insertion frequency in viable hematopoietic stem and progenitor cells (HSPCs).
The research revealed that CssDNA-edited HSPCs demonstrated superior performance compared to traditional viral approaches, showing "a higher propensity to engraft and maintain gene edits in a murine model than adeno-associated viruses (AAV)-edited HSPCs." This development addresses a key limitation in current gene therapy methods, which have been restricted primarily to gene corrections rather than broader therapeutic applications.
Over the past decade, non-viral DNA template delivery has been used with engineered nucleases to target single-stranded DNA sequences in HSPCs. Cellectis expanded this scope by developing an editing process using kilobase-long circular single-stranded DNA donor templates, potentially opening new avenues for gene therapy applications.
TALE Base Editor Safety Profile
In a separate presentation, Maria Feola, Ph.D., Senior Scientist and Team Leader Gene Editing at Cellectis, shared comprehensive safety data on TALE base editors (TALEB). These genome editing tools represent fusions of a transcription activator-like effector domain (TALE), split-DddA deaminase halves, and an uracil glycosylase inhibitor (UGI).
TALEB technology offers a unique advantage in genome editing by directly editing double-strand DNA, converting cytosine (C) to thymine (T) through uracil (U) intermediate formation without requiring DNA breaks. This approach has significant therapeutic potential, but safety concerns regarding off-target effects have been paramount.
The safety evaluation combined advanced bioinformatic predictions with multiple experimental approaches to investigate potential off-target effects in the nuclear genome of primary T cells. The study found "no evidence of biases towards off-site C-to-T editing at sites flanked by CTCF binding sites," a key DNA-binding protein that regulates genome organization and gene expression at the genome-wide level.
Implications for Therapeutic Development
These results provide what Cellectis describes as "a strong framework for the safe development of TALEB in therapeutic cell engineering, supporting their potential for future nuclear and mitochondrial applications." The safety profile data addresses critical regulatory and clinical development concerns that have surrounded base editing technologies.
The company's research was also featured as an oral presentation at the Homology-Directed Repair: The Path Forward Workshop, highlighting the scientific community's recognition of these advances.
Company Platform and Pipeline
Cellectis operates as a clinical-stage biotechnology company utilizing its gene-editing platform to develop cell and gene therapies. The company employs an allogeneic approach for CAR T immunotherapies in oncology, pioneering off-the-shelf and ready-to-use gene-edited CAR T-cells for cancer treatment, alongside platforms for gene therapies in other therapeutic areas.
With in-house manufacturing capabilities, Cellectis positions itself as one of the few end-to-end gene editing companies controlling the entire cell and gene therapy value chain. The company maintains headquarters in Paris, France, with additional locations in New York and Raleigh, North Carolina, and trades on both the Nasdaq Global Market (CLLS) and Euronext Growth (ALCLS).
