by Krystal Kasal, Phys.org

edited by Lisa Lock, reviewed by Robert Egan

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The VIPR targeting state forms a geometric triplex of nucleic acids. Credit: Science (2026). DOI: 10.1126/science.aei3472

CRISPR may be a powerful technology for gene editing, but the system existed in bacteria long before scientists began using it. For billions of years, CRISPR has acted as a natural immune system in bacteria and other microbes, helping defend them against invading viruses. But now, two new studies, published in Science, describe a similar RNA-guided system that originated in the viruses themselves and appears to be a precursor to CRISPR.

The search for CRISPR's origins

While scientists can manipulate these mechanisms to make precise changes to DNA to treat disease and improve crops, they still aren't sure exactly how the first CRISPR-like immune systems evolved. CRISPR systems use RNA guides to find matching DNA sequences and can be programmed by changing the sequence of the guide RNA. The origins of CRISPR's core RNA-binding proteins have been especially unclear.

The authors of the first study—most of whom are also involved in the second study—write, "CRISPR-Cas systems are divided into two classes on the basis of their effector proteins. Class 1 systems, the more abundant of the two, are thought to have evolved first. Their defining feature is the presence of repeat-associated mysterious proteins (RAMPs) that oligomerize on the CRISPR RNA (crRNA) to form the RNA-guided effector complex. RAMPs are among the most conserved and ancient features of CRISPR-Cas, proposed to date back to the last universal common ancestor."

The team decided to trace where RAMPs came from to find the evolutionary origins of CRISPR-Cas systems. Using a structure-based approach to search for RAMP-like proteins, the team identified an RNA-binding protein they call Viral interference programmable repeat (VIPR). VIPR was found in bacterial and viral genomes along with a small noncoding RNA, called vrRNA, which acts as the guide RNA.

Evolution of RNA-guided defense systems. Credit: Science (2026). DOI: 10.1126/science.ael0758

From VIPR to CRISPR

The team says that natural VIPR targets frequently occurred in rival bacteriophages, which are a specialized type of virus that exclusively infects, replicates inside and destroys bacteria. This seems to point to an ancient "arms race" between viruses. The researchers say that the VIPR system likely arose as a way for viruses to inactivate each other when competing for control inside the bacteria they had invaded.

The team thinks that bacteria may have co-opted VIPR systems used by invading viruses and adapted them for host defense. Eventually, this evolved into the CRISPR system found in bacteria. This proposed evolutionary link between VIPR and CRISPR is strongly supported, but there is currently no direct evidence. However, the team says that identifying intermediate systems between VIPR and class 1 CRISPR would further support this model.

The 'skip-one' code and future prospects

The team also found that VIPR uses an unusual "skip-one" code in which the guide RNA reads two DNA letters, skips one, then reads the next two. This was odd because, in CRISPR systems, the RNA guide matches its target in one continuous stretch. The guide RNAs in VIPR contain repeated units with conserved segments that the protein holds in place and variable segments that determine the DNA target.

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The team tested whether VIPR could bind DNA, silence a fluorescent reporter gene and block phage infection in E. coli. In the experiments, VIPR could be reprogrammed to silence selected genes and protect the bacteria from an invading phage. Structural images also showed that VIPR wraps RNA and both DNA strands into an unusual three-stranded shape, helping it pry open DNA.

The study authors explain, "Despite architectural parallels to CRISPR-Cas, VIPR systems unwind DNA by a mechanism distinct from known RNA-guided systems, which rely on base pairing–driven R-loop formation. Rather than invading the duplex through RNA strand exchange, VIPR systems use protein-driven triplex formation to unwind the DNA and enable RNA-DNA pairing."

The researchers say that the properties of VIPR systems make them the most minimal and potentially versatile platforms for RNA-guided DNA recognition ever encountered. They say that synthetic VIPR fusions could be used for genome editing, DNA locus imaging and epigenetic modification. Of course, there is still much work to be done as researchers gain a better understanding of VIPR and its evolutionary link to CRISPR. VIPR's unusual targeting logic could inspire new types of programmable genetic tools, and future work could reveal how VIPR guide-RNA libraries evolve and gain new targets.

Written for you by our author Krystal Kasal, edited by Lisa Lock, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You'll get an ad-free account as a thank-you.

Publication details

Peter H. Yoon et al, A noncontiguous code for RNA-guided DNA recognition at the origin of CRISPR-Cas, Science (2026). DOI: 10.1126/science.aei0498

Peter H. Yoon et al, VIPR RNA-guided DNA recognition by noncontiguous geometric triplex formation, Science (2026). DOI: 10.1126/science.aei3472

Jack P. K. Bravo, A viral origin for RNA-guided immunity, Science (2026). DOI: 10.1126/science.ael0758

Journal information: Science

Key concepts

bacteriavirusesEvolution, Molecular

Who's behind this story?

Krystal Kasal

Freelance science writer with Master's in physics. Five years clinical research and physics education experience. Science communicator. Full profile ?

Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile ?

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile ?