#Sweden #Stockholm #Gene Editing #Cellectis #Moligo

Introduction

In a remarkable breakthrough in the realm of biotechnology, Moligo Technologies, a trailblazer in DNA synthesis, has teamed up with Cellectis, a clinical-stage biotech firm, to showcase the potential of enzymatically synthesized single-stranded DNA (ssDNA) for non-viral gene editing. The findings, which were recently published in the prestigious journal Nature Communications, point towards a promising avenue for gene therapy that eliminates many of the risks associated with viral delivery methods.

The Study Overview

The collaborative study focuses on the efficacy of long ssDNA as a donor template for gene insertion in hematopoietic stem and progenitor cells (HSPCs). This method, co-developed by Moligo and Cellectis, stands out as a highly efficient solution for gene addition without the complications posed by viral vectors, which, while standard practice, carry inherent safety concerns and higher costs.

According to Dr. Cosimo Ducani, CEO of Moligo, the research conclusively demonstrates that their enzymatically produced long ssDNA vectors can replace viral systems as a scalable alternative for gene editing. He emphasized the significance of this milestone in advancing safer and more effective gene therapies accessible globally.

Challenges of Current Gene Editing Technologies

While viral vectors have been the go-to method for gene insertion in various cell types, their use is punctuated by significant drawbacks—the potential for unintended effects, high costs, and the risk of immune responses. Recently, researchers have begun experimenting with non-viral strategies, combining engineered nucleases with shorter ssDNA templates, but these methods had limited applications due to the length constraints on the DNA strands.

Moreover, traditional double-stranded DNA vectors face challenges including cytotoxicity and immunogenicity, which narrow their practical use. Moligo's innovative approach to enzymatic synthesis of long ssDNA overcomes these obstacles, paving the way for broader applications in gene therapies.

Key Findings

The groundbreaking study yielded several consequential findings:
1. Increased Efficiency: Moligo's ssDNA can achieve high levels of gene insertion in HSPCs, with the circular ssDNA format proving to be 3-5 times more efficient than linear counterparts.
2. Multiple Gene Targeting: These vectors allow multiple gene insertions in HSPCs, signifying adaptability for other therapeutic cell types, including primary T cells.
3. Enhanced Engraftment: Comparative analyses demonstrated that HSPCs modified with circular ssDNA showed a significantly higher ability to engraft and maintain gene edits in murine models compared to those modified with AAV6 vectors.

Implications for Future Therapies

The implications of these findings are vast, establishing the circular single-stranded DNA (CssDNA) and TALEN® editing processes as viable non-viral strategies for gene insertion. Julien Valton, Vice President of Gene Therapy at Cellectis, stated that this development indicates a crucial step toward realizing next-generation cell and gene therapies.

About Moligo Technologies

Founded in 2019, Moligo Technologies excels in producing long, ultra-pure DNA through a proprietary enzymatic synthesis process, overcoming limitations traditionally associated with chemical methods. Their innovative technology enables the production of substantial quantities of DNA, which is critical in advancing various cell and gene therapies through clinical trials and into patient care.

About Cellectis

Cellectis, headquartered in Paris, is at the forefront of clinical-stage biotechnology, leveraging its unique gene-editing platform in the development of CAR T-cell therapies for oncology and other therapeutic areas. Their commitment to off-the-shelf, allogeneic CAR T products stands testament to their innovation in addressing cancer treatment needs.

Conclusion

With this collaboration, Moligo Technologies and Cellectis are not just advancing gene editing techniques but are also reinforcing the importance of strategic partnerships in driving innovation in the biotechnology sector. The shift towards safe, efficient non-viral gene therapies holds the promise to transform how diseases are treated, making therapies more accessible and effective for those in need.