A team of researchers at UC Berkeley and UCSF has successfully engineered a new CRISPR-based technique that can selectively destroy cancer cells.
The study, published Monday in the journal Nature, differs from traditional CRISPR gene-editing tools, which act as molecular “fixers” or “editors.” This approach, on the other hand, uses a specialized enzyme that acts as a precise “destroyer,” completely shredding the genetic material of mutated cells.
The engineered enzyme, known as Cas12a2, was derived from bacterial communities, which developed this evolutionary adaptation to survive virus infections. In its natural bacterial state, the enzyme functions as a “suicide pill,” destroying the infected cell’s entire genetic material upon detecting a viral infection to protect the wider bacterial population.
The research team successfully used this mechanism to recognize cancer-specific RNA sequences. Once the specific target mutation is sensed, the enzyme activates its secondary function, which cuts all the DNA randomly in the cell and shreds the chromatin into pieces, triggering cell death.
“When we talk about cancer, people maybe just think about, there’s a particular mutation that drives malignancy,” said Jingkun Zeng, a postdoc at UC Berkeley’s Innovative Genomics Institute and the study’s first author. “But in reality each cancer cell can have hundreds of thousands of mutations at late stage, so at that point you can’t fix it anymore … It’s just best to kill them.”
The method was said to have an exceptional level of specificity, capable of distinguishing between a healthy cell and a cancer cell based on small differences in their RNA sequences.
“It establishes a principle that we can now target almost any genetic change in cancer,” said Alan Ashworth, co-author of the study and president of the Helen Diller Family Comprehensive Cancer Center at UCSF.
The discovery grew out of a joint project within the CRISPR Cures for Cancer initiative, an inter-institutional partnership between UCSF, the Gladstone Institutes and the IGI at UC Berkeley, along with collaborators at the University of Utah and Utah State University.
“I don’t want to claim we cured cancer here,” Ashworth said. “But the first step in any new therapy is a new idea — a new concept — and technology is what drives forward developments in science generally, in medicine, and in cancer research. So that’s why I’m so thrilled by a new approach.”
Despite the excitement, the technology is still in early phases and faces substantial limitations, particularly regarding delivery. Because the enzyme is very large, it cannot be taken orally.
To overcome this, Niren Murthy, a professor in the UC Berkeley Department of Bioengineering and an author of the paper, whose lab led the study’s delivery effort, is developing other solutions to allow the large enzymes to enter cells safely, a strategy that was successfully tested in the lungs.
“I’m very excited about the possibility of trying to develop this into a clinical treatment for cancer and perhaps for other types of diseases,” Ashworth said.
With hopes that, with more work, the team’s research can ultimately move toward clinical trials, according to Zeng.
The paper cited 25 authors across these multiple institutions.
“We did it in such a lovely collaborative way, and it will continue to be a collaboration,” Ashworth said. “It shows the power of different people working together, and what two fantastic universities we’ve got.”