CRISPR Variant Selectively Targets Tumor DNA

A research team from the Van Andel Institute and Wageningen University & Research has developed a method to distinguish tumor DNA from healthy DNA using a specific CRISPR variant, allowing for the selective cutting of malignant genetic material.

The study, published April 15, 2026, in Nature, describes the use of a CRISPR variant known as ThermoCas9 to achieve this precision. This development represents an early step toward the creation of high-precision cancer therapies designed to destroy tumor cells while leaving healthy cells intact.

The Role of DNA Methylation

The ability to differentiate between healthy and cancerous cells relies on identifying subtle chemical differences. The researchers focused on methyl groups, which are small chemical tags attached to DNA that regulate whether specific genes are turned on or off.

This process, known as DNA methylation, is altered in cancer cells. These alterations create a molecular fingerprint that allows the CRISPR variant to distinguish malignant cells from healthy ones.

Precision Editing with ThermoCas9

The team utilized ThermoCas9, a CRISPR variant that was discovered in bacteria several years ago by Dr. John van der Oost of Wageningen University & Research. Like other CRISPR systems, ThermoCas9 can be programmed to locate and cut specific sections of DNA within a cell.

By leveraging the distinct methylation patterns of tumor DNA, the team led by Dr. Hong Li of the Van Andel Institute and Dr. Van der Oost was able to program the system to selectively target and cut the DNA of tumor cells.

The research involved a collaborative effort, with members of Dr. Li’s lab serving as co-first authors of the study published in Nature.

Implications for Cancer Therapy

Cancer cells are often difficult to treat because they excel at evading detection by the immune system and other medical interventions. The ability to exploit chemical differences like DNA methylation provides a potential pathway for more accurate targeting.

Because the ThermoCas9 variant can selectively cut tumor DNA without affecting healthy DNA, the method offers a promising foundation for future therapies that aim to increase precision and reduce the impact on non-cancerous tissues.

While these findings are described as a promising step, the researchers characterize the study as an early stage in the development of these potential therapies.