Jennifer Doudna's Lab Discovers VIPR, a Likely Evolutionary Ancestor of CRISPR Found in Viruses, and Has Already Reprogrammed It

Jennifer Doudna's Lab Discovers VIPR, a Likely Evolutionary Ancestor of CRISPR Found in Viruses, and Has Already Reprogrammed It
On September 17, 2026, Science published two papers from the laboratory of biochemist Jennifer Doudna (University of California, Berkeley) describing VIPR, a family of viral proteins that are primitive relatives of CRISPR-Cas proteins, encoded mainly in viral rather than bacterial genomes. The team deciphered how the system recognizes DNA and has already reprogrammed it to silence genes and protect cells from viral infection.

CRISPR-Cas are the "genetic scissors" that bacteria use as a defense against viruses and that Doudna and colleagues turned into a gene-editing tool, earning the 2020 Nobel Prize in Chemistry. The origin of the mechanism remained unclear: its most ancient component retains almost no gene-level similarity across species, and gene-based searches could not find its ancestors.

Doudna's graduate student Peter Yun proposed searching not by gene sequence but by protein shape: three-dimensional structure is conserved over billions of years, even when the underlying gene has changed beyond recognition. "Nature is very lazy," he told The New York Times. The approach already had precedent: two years earlier, the team used it to find an ancestor of a different CRISPR protein. This time they ran the search across 2.3 million protein structures and found hundreds of similar proteins, most of them from bacteriophage genomes. "It was a complete reversal of our expectations."

The team named the system VIPR. When a phage carrying VIPR infects a bacterium, this segment of its genome produces short RNAs: together with the Vipr protein, they recognize a DNA target in a way that differs from CRISPR, skipping every third base. The skipped base typically falls at a position in the gene where a virus can mutate silently without altering the encoded protein, and because VIPR does not read that position, such an escape mutation cannot fool it. Unlike most CRISPR tools, VIPR does not require a recognition motif near its target, and the protein itself is several times more compact.

The system's functionality was demonstrated using phage SUSP1, which had been stored in the laboratory freezer. "We got very lucky," recalls co-author Kenneth Loy. "We just thawed the virus, infected some cells, and said: let's see what we find." By reprogramming the RNA, the researchers made VIPR silence a chosen gene, protect a bacterium from a phage, and reawaken a dormant virus. The natural targets confirmed the hypothesis about VIPR's origins: in one lineage, 18 out of 20 targets mapped to genes of a competing satellite phage, indicating that VIPR serves as a weapon in a war between viruses inside the infected cell.

This gives rise to a hypothesis about the origin of CRISPR: bacteria captured this viral weapon and, by coupling it to an enzyme that integrates foreign fragments into the genome, gained heritable immune memory. "It all starts to make sense," Doudna says. "It's something like an ancient war between viruses."

The authors have shown that VIPR can be made to silence genes, protect a cell from a phage, and awaken a dormant virus, but it cannot cut or insert DNA, let alone work in human cells. They describe the finding as the discovery of a new principle of DNA recognition, not a ready replacement for CRISPR. The University of California has already filed a patent application covering VIPR-based technologies. Rafael Pinilla-Redondo, a virologist at the University of Copenhagen who was not involved in the work, expects more to come: "I would be very surprised if VIPR turned out to be the last unexpected recognition system we discover."