Biotech investors: Stop expecting CRISPR science to make big leaps

ORIGINAL SOURCE: STAT

Despite the power of this new tool, it’s going to take time to develop its full potential

By Kelly Banas and Eric B. Kmiec April 14, 2025 - The medical promise of CRISPR gene editing can be seen most easily in current research on oral cancer, which affects more than 50,000 Americans every year. An increasing challenge in the treatment of oral cancer is that tumors become resistant to chemotherapy. By injecting CRISPR gene editing directly in the tumors and targeting the genetic resistance to common chemotherapy agents, we could potentially enable that standard of care for cancer to work once again for patients, overcoming one of the toughest hurdles in treatment today. In doing so, we may improve outcomes for a disease whose demographics skew toward low-income communities.

CRISPR is not a miracle product that can magically cure cancer. It is, however, an exceptionally powerful tool that is creating entirely new possibilities in cancer treatment.

As scientists, we have taken on the drudgery of understanding the mechanism of action of CRISPR-directed gene editing and how to apply it. These studies often do not make a splash in the field and are almost never presented at major meetings, yet they provide guidance as to how best to harness the power of this technology. The outcome is not always what we want; we would love to cure systemic diseases by repairing the mutations that causes them. But at this point in the science, big leaps are simply not practical.

Yes, it took us a decade to learn that despite the power of this new tool, it’s going to take time to develop its full potential. In this still-early world of gene-editing research, studies that determine how the concept can have therapeutic effect, respecting and expanding on the limitations of current knowledge, are passed over for funding because they lack big-bang glamor. Investors are looking for the big home-run hitters, while those with more modest scientific goals are, more often than not, the ones who deliver.

Consider Tome Biosciences, which launched in December 2023 with more than $200 million in funding. The company burned through all of its funding in less than one year and failed to capitalize on the promising gene-editing platform its founders had developed to address genetic diseases like muscular dystrophy. But this task involved difficult science. Precision is key to gene-editing events, but the process is not yet precise. We use that lack of precision for broad strokes delivered at the site of the tumor, but Tome’s pursuit of a systemic cure had a much narrower window of opportunity.

Tome’s rise and precipitous fall is not atypical. Over the past year, at least a half dozen CRISPR-focused biotech startups have shrunk operations and laid off employees.

In this field, too many companies are inches away from each other, conceptually. Investors appreciate this and often channel their resources in the same direction because there’s safety in numbers. The similarity of the work also means that experiments performed in one of these labs can be duplicated in another facility with similar resources.

There is a difference, however, between reproducibility and robustness. Reproducibility is the easy standard. But robustness means that researchers outside of the biotech corridors, or even those in the Global South, can use their equipment, their resources, and generate similar results. This robustness is what we are missing in the CRISPR company world, in part because it is not appreciated.

Robustness is central to the ultimate goal of curing patients of the diseases that afflict them. All too often, companies prioritize building a patent portfolio to accumulate intellectual property, just to please investors. What the developments mean for the patients, at the end of the day, are secondary or even tertiary.

Consider the success of Casgevy, the first CRISPR therapy to be approved for patients, in this case for those suffering from sickle cell disease — a disease mostly affecting African American communities. Casgevy is still not a miracle pill; instead, stem cells are extracted from patients, their genomes are edited using CRISPR technology, and then the edited cells are transplanted back into patients. The cure is miraculous, but the treatment remains a difficult process.

Indeed, the recent wave of layoffs and financial troubles at CRISPR-focused startups should not tarnish the promise of CRISPR. CRISPR technologies still have tremendous potential to improve the health of patients with hard-to-cure or incurable illnesses. There are many valuable wins we can achieve for patients suffering from the most intractable cancers, where the science advances in small, non-glamorous increments yet the lifesaving impact for patients could not be more significant.

The market gyrations are an indictment of how venture capital tends to look for the next really big thing instead of focusing on starting small and slowly building on victories to support patients and their health. Long-term focus is key to success — and we as researchers must define this success as our benchmark, in all of our operations and when soliciting funding.

Kelly Banas, Ph.D., is associate director of research at the Gene Editing Institute at ChristianaCare. Eric B. Kmiec, Ph.D., is founder and executive director of the Gene Editing Institute at ChristianaCare.