University of Utah team develops Cas12a2 enzyme that destroys virus-infected cells

Researchers at the University of Utah, led by Ryan Jackson of the Center for Biochemistry, reported on May 20, 2026 in Nature that the recently discovered CRISPR protein Cas12a2 can selectively destroy virus-infected or cancer cells while sparing healthy cells.

The finding extends CRISPR applications from precise gene editing to targeted destruction of pathological cells. It opens a path to a potential new class of antiviral drugs and immunotherapies for hard-to-treat tumours. The mechanism was first demonstrated in human cell cultures infected with dengue virus, and in samples from a glioblastoma cell line.

What Cas12a2 is and why it differs

Cas12a2 is a recently described variant of the CRISPR protein. Peter Fineran’s team in New Zealand initially characterised it in 2023.

Unlike classical Cas9 or Cas12a, which make precise cuts in DNA at defined sites, Cas12a2 exhibits two activities:

• recognition of a target sequence
• non-specific cleavage of all surrounding DNA and RNA in the cell

That sounds destructive, but this very property allows selective destruction of only those cells that contain the target signal, for example a viral RNA or a tumour-specific mutation. Healthy cells without that signal do not activate the enzyme and remain unharmed.

Methodology and preliminary results

In the experiments published in Nature, Jackson’s team engineered Cas12a2 to recognise a conserved sequence in the dengue virus genome.

Results of the cell-culture tests:

• in human hepatocytes infected with the virus, more than 92 percent of infected cells were destroyed within 24 hours
• less than 1 percent of healthy cells showed any adverse effect
• in glioblastoma cell lines with a specific EGFRvIII gene mutation, about 78 percent of tumour cells were eliminated
• surrounding healthy neuronal cells remained functionally intact

The key challenge is delivering Cas12a2 only into cells that have a potential target. The team currently does this using lipid nanoparticles and adenoviral vectors. Both approaches have limitations. Lipid particles accumulate mainly in the liver, while adenoviral vectors trigger an immune response that erodes effectiveness over time. The authors note that developing more efficient delivery systems is the biggest barrier to moving from laboratory to clinical practice.

What the study does NOT show

The results are encouraging, but they come exclusively from cell cultures. No experiment was conducted in animal models, which is a required step before considering human clinical trials.

Dengue virus was chosen as the test system because of its relatively simple genome structure. Larger viruses, such as HIV or hepatitis B, have more complex mechanisms of integration into cellular DNA, which may rule out the same approach. For cancers the problem is more complex still, because many tumour cells do not carry clearly defined mutations that can be used as exclusive targets.

A second important limitation is that Cas12a2 can show off-target activity in rare cells that happen to contain a similar sequence. The team recorded side effects in about 0.8 percent of healthy hepatocytes. That is low, but not negligible for future clinical applications.

The next step in the research is a long-term experiment in mice with chronic viral infection. The aim is to show whether the therapy can be sustained over multiple weeks of treatment.

Relevance for Serbian virology

The research is significant because it opens a potential alternative approach to treating viral diseases for which there are no effective drugs at present. That includes some arboviruses that are increasingly appearing in Serbia due to climate change.

What is a realistic timeline for the first clinical use of this technology, five years or fifteen?

Tell us what you think: is this kind of therapy a promising alternative to conventional antiviral drugs? Leave a comment below.