Advancing CRISPR: Caszyme Collaborates with Integra Therapeutics
We find out why Cas12l incorporated into a gene-writing system could help advance the field of gene editing.
| 4 min read | Interview
After years of collaboration, Caszyme, a developer of CRISPR gene-editing technologies, has entered into a partnership with Barcelona-based Integra Therapeutics. The agreement focuses on incorporating Caszyme's Cas12l genome editor into Integra’s FiCAT 2.0 platform, a gene-writing system designed for advanced gene and cell therapy applications. The companies hope that the collaboration will enhance precision and efficiency when editing and inserting genetic material. Cas12l is known for its compact size and high specificity, which may enable better targeting of genetic sequences and minimize off-target effects. These improvements could lead to more reliable and effective gene and cell therapies.
I visited Caszyme’s laboratories in Vilnius, Lithuania, in 2023, where I learned about the industry-wide excitement surrounding CRISPR technology directly from Caszyme CEO Monika Paule and her colleagues, as well as the incredible responsibility that comes with it. After learning about the new collaboration, I caught up with Paule again to find out more.
Why are the companies a good fit for one another?
Ultimately, we hope to accelerate the development of next-generation gene-editing therapies. By out-licensing our novel nucleases, we can increase the availability of CRISPR-Cas tools and enable their application across diverse therapeutic areas.
Caszyme’s strength lies in its expertise in CRISPR technology, particularly in the discovery and development of novel molecular tools. We have extensive experience in protein evolution, mRNA optimization, and the engineering of customised Cas nucleases. This know-how enables us to deliver innovative, efficient, and precise solutions tailored to specific therapeutic needs.
Integra Therapeutics, on the other hand, specializes in advancing its gene-writing tools. Our novel nucleases perfectly complement Integra’s FiCAT platform, fostering a seamless synergy between our technological expertise and their therapeutic focus. Together, we hope to streamline the progression of gene-editing technologies and accelerate the transition from the laboratory to clinical applications.
What are the advantages of Cas12l nucleases over other CRISPR nucleases?
Cas12l is a unique and versatile CRISPR nuclease family with an effector size of approximately 850 amino acids. This small size addresses a key challenge in therapeutic gene editing: efficient delivery to cells and tissues, particularly via vectors with limited cargo capacity, such as AAVs, mRNA, and LNPs.
Caszyme-developed Cas12l nucleases combine the compact design with efficacy comparable to larger nucleases, such as Cas9. They also have demonstrated great activity in human cells across multiple targets, underscoring the strong therapeutic potential. We are very excited about the delivery possibilities, especially when paired with other effector domains. Moreover, smaller nucleases from non-pathogenic bacteria may be less immunogenic than their larger counterparts, further highlighting the potential for clinical use.
What are the anticipated milestones and when might we expect to see clinical applications?
A significant milestone to anticipate is the completion of our joint Eurostars translational project, expected to conclude in 2025. This project will provide crucial preclinical data that will drive the upcoming phases of development. Following the successful preclinical outcomes and IND approval, Integra is expected to transition to clinical trials within a few years.
Developing therapies with Cas12l nucleases involves navigating stringent regulatory requirements, as is typical for gene-editing technologies. These challenges are compounded by the limited clinical data currently available on Cas12l. To address these hurdles, we are focusing on generating preclinical data to demonstrate specificity, safety (including off-target effects), and efficacy of Cas12l nucleases.
Do you plan to pursue more licensing agreements with other companies?
Absolutely! We see tremendous potential in Cas12l nucleases for advancing new therapies. Licensing agreements are key to making these powerful molecular tools more accessible, giving our partners the ability to push the boundaries of what’s possible in therapeutic innovation.
By enabling treatments across diverse therapeutic areas, these tools could address a wide range of diseases. Collaborating in this way opens the door to targeting more conditions, tackling unmet medical needs, and ultimately bringing next-generation therapies to more patients.
These licensing partnerships are essential for maximizing the impact of the technologies we’ve developed. They help us drive transformative treatments forward, ensure global accessibility, and contribute to solving some of the most pressing challenges in healthcare today.
How do you envision this collaboration accelerating the development of gene-editing therapies, and what potential impact could it have on patient outcomes?
This partnership with Integra Therapeutics represents an important step in bringing advanced molecular tools like Cas12l nucleases closer to clinical use. It connects innovative CRISPR-Cas technologies with real-world therapeutic applications, helping to bridge the gap between research and treatment. Early preclinical results with Cas12l have been promising, and I hope that these findings will translate into successful clinical trials.
By improving precision and efficiency in treatments for conditions that conventional medicine has struggled to address, this collaboration has the potential to make a meaningful difference in patient outcomes. For individuals who currently have few or no treatment options, it could represent a significant step toward better quality of life and a broader range of therapeutic possibilities.
