Jennifer Doudna’s team found an ancient CRISPR ancestor in viruses using a never-before-seen ‘gapped’ DNA code; the smaller VIPR system can target broadly and may become a new gene-editing tool
The genetic code is usually described as an orderly language, read one letter after another in precise three-letter units. But nature has never been particularly interested in following the rules humans use to describe it. Researchers at the Innovative Genomics Institute (IGI), founded by Jennifer Doudna, have now uncovered a viral system that appears to rewrite some of those assumptions. Called VIPR, the system uses a previously unknown “gapped” coding strategy to recognise DNA, offering clues about the ancient origins of CRISPR and potentially opening another route to genome engineering. The findings were reported in two connected papers in Science in September 2026.
A mystery hidden in viral RNA
The discovery began with a search for ancient relatives of Class 1 CRISPR systems, the older and more widespread branch of CRISPR biology. Unlike the better-known Cas9 system, Class 1 systems rely on several proteins working together.Researchers Peter Yoon and Kenneth Loi used AI-assisted structural analysis to screen roughly 2.3 million protein structures. Among hundreds of candidates, one stood out because its shape resembled proteins associated with ancient CRISPR systems, even though it was paired with an unfamiliar RNA rather than a recognisable CRISPR guide.The RNA initially appeared almost impossible to interpret. Its sequence contained repeating patterns that conventional genetic analysis did not explain.
The code between the gaps
A second AI approach helped reveal the pattern. The researchers found that groups of three bases repeatedly contained a predictable pair followed by a highly variable third position. Instead of reading the sequence continuously, the system appeared to skip across it, effectively creating a hidden code. That pattern ultimately allowed the researchers to identify matching sequences in viral DNA.The finding is unusual because genetic information is generally interpreted as a continuous sequence. VIPR instead appears to ignore positions that are more prone to mutation while concentrating on more stable parts of the genetic code. This could give the system an advantage when targeting rapidly changing viral genomes.
A different way to engage DNA
VIPR also behaves differently from familiar CRISPR systems. Rather than using a protein to cut DNA, researchers found that its RNA can wrap around the DNA double helix, forming a three-stranded structure known as a triplex. That interaction can interfere with gene activity rather than cutting the DNA itself. In laboratory experiments, the researchers were able to reprogram VIPR to bind near a gene’s promoter and silence the gene.The system is also remarkably small. Its compact size could be useful because delivering large genome-editing machinery into cells remains a major challenge in developing practical gene-editing technologies. The IGI itself identifies delivery as one of the biggest barriers to broader use of CRISPR-based therapies.
A viral origin story for CRISPR
The discovery may also reshape ideas about where CRISPR came from. The researchers found VIPR systems in viruses that appear to use them against competing viruses, suggesting that viral competition helped shape this unusual molecular weapon.Even more intriguingly, some functional VIPR systems appear to have moved into bacteria. The researchers propose that bacteria may have acquired such viral machinery and repurposed it against viruses, potentially contributing to the evolutionary pathway that eventually produced ancient Class 1 CRISPR systems.For now, VIPR remains a research tool rather than an established medical technology. But its unusual structure, tiny size and broad targeting potential give scientists another piece of the evolutionary puzzle, and another molecular system to explore as the genome-editing toolbox continues to expand.Images Courtesy: UC Berkeley Research
