The history of CRISPR appears to begin far earlier than we thought. Researchers from the University of California, Berkeley, and the Innovative Genomics Institute have discovered in bacteriophages an ancient molecular system, VIPR — Viral Interference Programmable Repeat — which may have existed even before the first CRISPR-Cas systems appeared.
Two related papers were published on 17 September 2026 in the journal Science. Evolutionary analysis shows that VIPR proteins are related to the most ancient components of CRISPR and are probably closer to their evolutionary origins. This supports an unusual hypothesis: some of the mechanisms from which bacterial CRISPR immunity later arose may originally have been weapons of the viruses themselves in their struggle against one another.
A genetic code with gaps
The most unusual feature of VIPR is its method of DNA recognition.
Conventional RNA-guided systems match a guide RNA against a target sequence almost continuously. VIPR works differently: its RNA recognizes DNA not as a continuous sequence, but at regular intervals.
In effect, when recognizing a target, the system can ignore every third position of the DNA. It is precisely the third letter of a codon that is often the most variable and in many cases can mutate without changing the amino acid.
The result is a kind of molecular filter: VIPR pays attention to the more stable part of the sequence and skips positions that change more easily. This potentially makes it harder for a virus to evade recognition through mutations.
There is another oddity as well. VIPR interacts with the DNA double helix in a way quite unlike familiar CRISPR systems. Structural studies have shown that the complex forms an unusual structure around the DNA involving both RNA and DNA — a kind of molecular triple helix.
Viral interaction long before CRISPR
Analysis of VIPR's natural targets shows that bacteriophages carrying this system often direct it against other phages infecting the same hosts.
In other words, VIPR was probably originally part of an ancient molecular interaction — "virus against virus."
The authors suggest that later bacteria may have borrowed components of such systems and turned them into their own defense against viruses. From this ancient exchange of molecular weapons, early CRISPR-Cas systems may have gradually emerged.
How long ago this happened cannot be determined directly. The researchers link the origin of these mechanisms to very early stages in the evolution of cellular life — possibly even before the last universal common ancestor of modern organisms. So we may indeed be talking about events that took place billions of years ago, but the exact age of VIPR remains a hypothesis for now.
A new tool for genetic engineering?
VIPR is interesting not only as an evolutionary find.
Its protein component is very compact, and to recognize a target the system does not require an adjacent PAM sequence — a constraint characteristic of, for example, Cas9. This potentially expands the number of DNA sites at which the system can be aimed.
Scientists have already shown that VIPR can be reprogrammed so that it binds to a chosen DNA site and suppresses the work of a gene.
VIPR is not yet a new ready-made CRISPR analogue for editing the human genome. In the published experiments, the system primarily recognizes DNA and regulates gene activity; its capabilities for full-fledged editing, epigenetic interventions or therapy have yet to be tested.
And yet the discovery changes the view of the origin of one of the most important tools of modern biology.
CRISPR turned out to be not the beginning of the story, but one of its later chapters. Behind it was discovered a more ancient molecular architecture — created not by humans and, possibly, not even by bacteria, but by viruses that, billions of years ago, were already learning to recognize the genetic sequences of their rivals.
Looking deeper into evolution, we discover not primitive drafts of nature, but technologies whose principle of operation we are only beginning to understand.
