Berkeley researchers identify ancient viral ancestor of CRISPR

Researchers at the University of California, Berkeley have identified a genome-editing system found in viruses that they say predates CRISPR, the technology already used to treat sickle cell disease.

The system, named VIPR, was described in two papers published in the journal Science on Sept. 17, 2026, by researchers from professor Jennifer Doudna’s group at UC Berkeley’s Innovative Genomics Institute, according to the institute.

Kenneth Loi, a graduate student in Doudna’s group and a first author on one of the studies, and former graduate student Peter Yoon led the work identifying and reprogramming VIPR, according to the Daily Californian. Terry Zhang, another Doudna lab graduate student, and Trevor Docter, formerly of professor Stephen Brohawn’s lab, worked on a companion paper describing VIPR’s structure and biochemical mechanism, published the same day.

Like CRISPR, VIPR functions in nature as part of a defense system that microorganisms use to read and remember the genetic sequences of invading viruses. But where CRISPR-Cas9 tracks an entire continuous sequence of a target’s genetic code, VIPR reads only scattered snippets of it, using what the Innovative Genomics Institute describes as a “skip cipher”: pairing two bases, then skipping the third, mutation-prone “wobble” position.

That gapped recognition could let VIPR keep identifying viruses, or other fast-mutating targets, even as the rest of their genetic sequence changes, according to Loi. “There are certain types of targets that mutate very rapidly, and in those cases you can imagine … they would eventually mutate away and prevent CRISPR from being able to recognize it,” Loi said, according to the Daily Californian. “In VIPR’s case, you can imagine if you target that same target site, it might be more robust to whatever mutations arise.”

Loi said he sees potential for VIPR in targeting cancers that mutate quickly enough to escape existing CRISPR-based treatments.

Mechanically, CRISPR-Cas9 pries the two strands of the DNA helix apart to cut its target. VIPR instead wraps around the double helix, forming a three-stranded structure that silences a gene rather than severing it, according to the Innovative Genomics Institute. The institute describes VIPR as the smallest RNA-guided system yet found, and one that, unlike CRISPR-Cas9, does not require a short neighboring sequence called a PAM to locate its target, a restriction that limits where existing CRISPR tools can act.

Loi said he and Yoon spent 14 months trying to work out what the system did. “It was very non-obvious what (VIPR) even does. All we could tell was that … it’s related (to CRISPR),” Loi said, according to the Daily Californian. “It was 14 months of just that, me and Peter working full time … when we finally cracked the code, it was electric.”

Doudna said the team found VIPR by searching for proteins with a particular shape rather than a particular genetic sequence, using AI-based structural comparison tools to scan roughly 2.3 million protein structures, according to the Innovative Genomics Institute. “If you want to find something truly ancient, you need to look for something with a particular shape, not a particular sequence,” Doudna said. She described the early stage of the project as puzzling: “We were scratching our heads. It didn’t look like any RNA we had ever seen before. That’s where the project was stuck for months.”

The researchers’ findings suggest VIPR originated in viruses and was later acquired by bacteria, which turned it into a defense against other viruses, an event the Innovative Genomics Institute says predates the emergence of Class 1 CRISPR-Cas systems. The papers, titled “A Noncontiguous Code for RNA-Guided DNA Recognition at the Origin of CRISPR-Cas” and “VIPR RNA-guided DNA recognition by noncontiguous geometric triplex formation,” concluded that “CRISPR-like immunity evolved from ancient conflicts between competing viruses,” introducing what the authors called a new programmable tool for controlling gene expression.

Noah Whiteman, a UC Berkeley professor who uses CRISPR to study the evolution of biological traits, said the discovery points to editing capabilities beyond what CRISPR currently offers and that other researchers are likely to move quickly to apply it. “I’m sure very soon people are probably getting components of (VIPR) and trying to get it to work. So I would imagine very, very soon you’re going to see papers come out that implement (VIPR),” Whiteman said, according to the Daily Californian.

Doudna said the discovery points to how much about basic biology remains unknown: “This work is a great reminder of how complex biology is, and how little we still know,” she said, according to the Innovative Genomics Institute.