Mammoth Biosciences is a biotechnology company focused on developing in vivo gene-editing therapeutics using proprietary ultracompact CRISPR systems to create potential long-term curative therapies for life-threatening and debilitating diseases.
What are the most exciting developments for Mammoth’s CRISPR technology platform from the past year?
The biggest development for us has been advancing what we call non-double strand break techniques or “CRISPR plus,” which go beyond traditional gene editing. These include innovations like base editing, gene writing, and epigenetic editing. Essentially, we are developing ways to edit any part of the genome. Imagine treating the genome like a Word document, where you can bold, italicize, add, or delete as needed.
The major challenge, though, is delivering these edits to critical areas like the brain or muscles, as most current gene editing targets blood or liver tissue. The original CRISPR systems, like Cas9, are physically too large for delivery systems that reach these other tissues. Our focus has been on miniaturizing CRISPR so it can work with non-double strand break techniques and reach areas where most genetic diseases occur, truly unlocking the potential of genetic medicine.
What does your new partnership with Regeneron mean for you and for CRISPR technology?
Partnering with Regeneron is incredibly exciting for us. Regeneron has invested significantly in genetic medicines, particularly in advanced delivery systems like AAVs, which are essential for targeting tissues beyond the liver or blood. However, AAVs have limited capacity and can only carry small payloads, so having tiny CRISPR systems is crucial to make full use of their technology.
This partnership brings together our unique capabilities in creating small CRISPR systems with Regeneron’s expertise in delivery systems and disease insights. Working with Regeneron, a leader in biotech, is also inspiring; they have paved a path we aspire to follow, demonstrating how strategic partnerships can help build a successful biotech company. We are thrilled Regeneron will be part of our journey.
When can patients expect to see the benefits of CRISPR, given how long the field has been developing?
CRISPR is already making strides, with Casgevy’s recent approval for treating sickle cell disease marking a significant milestone. The exciting aspect of CRISPR as a platform technology is that it should get faster and more reliable with each successive approval, creating a “flywheel” effect in development.
Initially, most new therapies will target the blood and liver, where current delivery systems work best. At Mammoth, however, we are looking beyond that, aiming to reach tissues that are harder to treat but have high unmet needs. Although 10 years might seem long, in biotech, it is actually a rapid timeline for a platform’s first approval. Looking forward, I think we will see CRISPR therapies approved even faster than with previous biotech advancements.
Do you think AI will accelerate CRISPR’s path to clinical applications?
Absolutely. From the beginning, we have integrated AI and machine learning across our operations, particularly in protein discovery and engineering. The key to effective AI application is having robust data, and Mammoth is uniquely positioned with the largest database of metagenomic data in this field, complemented by our high-throughput experimental capabilities.
We have an entire floor of liquid-handling robots that allow us to generate large-scale, high-quality data. This setup gives us a distinct advantage in optimizing AI models to design CRISPR proteins, setting us up to fully leverage advances in AI for more precise and efficient genetic editing.
When will we know more about the specific diseases Mammoth is working on?
While much of our pipeline remains confidential, some exciting developments are already public. Our lead program targets familial chylomicronemia syndrome, a severe condition causing high triglycerides that lead to pancreatitis. By knocking out a specific gene, we can lower triglycerides, offering a potentially curative single-injection treatment, as opposed to the current zero-fat diet that is very challenging for patients.
This program is just one of many. We also work extensively with partners like Regeneron, Vertex, and Bayer, who bring deep expertise and funding, allowing us to maintain one of the most diverse pipelines in the CRISPR space.
How has your focus on diagnostics shifted since the pandemic?
During the pandemic, we demonstrated the potential of CRISPR-based diagnostics, but strategically, we have since shifted to focus fully on therapeutics. We realized that diagnostic demand would not sustain post-pandemic at the same level, so our resources are now directed toward becoming a biotech therapeutics company.
We still believe in CRISPR-based diagnostics and partner with others interested in developing products in this area. Essentially, we aim to be the “Intel inside” for CRISPR diagnostics, providing foundational technology while focusing our own efforts on therapeutic applications.
Do you think the public is becoming more comfortable with gene editing? Are there concerns about its potential dangers?
Yes, and I think the comfort comes largely from the fact that gene editing is targeting severe, life-altering genetic diseases with substantial unmet needs. Patient advocacy groups often actively push for these advancements, understanding the immense impact these therapies could have on their lives.
While we can imagine controversial uses in the distant future, the current focus on curing serious genetic diseases is more of a “no-brainer.” With thousands of genetic diseases left to address, the therapeutic promise alone will keep us occupied for decades before even considering other applications.
Looking forward, what progress do you hope to see in the gene editing space in the next year?
By this time next year, I hope we will be discussing more approved CRISPR drugs that are making a tangible difference in patients’ lives. We also expect to see breakthroughs in delivering complex genetic editing techniques to tissues beyond blood and liver, addressing those areas with high unmet needs.
In the next decade, I am optimistic we will see dozens of CRISPR-based therapies available, especially as we tackle diseases outside the traditional low-hanging fruit like liver and blood disorders. Mammoth is ready to help make that future a reality.
