Scientists discover VIPR, a gene-editing system older than CRISPR

Scientists have identified a gene-editing system believed to be over four billion years old, one that may have given rise to CRISPR and could eventually surpass it as a tool for modifying DNA. The system, called VIPR — short for Viral Interference Programmable Repeat — was described on Thursday in two papers published in the journal Science.nytimes+1

An Ancient Viral Defense

Unlike CRISPR, which was found in bacteria, VIPR originates from viruses that use it as a weapon against competing phages. A team led by Jennifer Doudna, the University of California, Berkeley biochemist who shared the 2020 Nobel Prize in Chemistry for her work on CRISPR, identified the system after years of investigating the evolutionary origins of RNA-guided immunity.biorxiv+2

According to the researchers, VIPR consists of a Vipr protein that is ancestral to the earliest CRISPR-Cas effectors, paired with specialized VIPR RNAs, or vrRNAs, that use alternating molecular motifs to recognize and bind to DNA. A companion study detailed 21 cryo-electron microscopy structures showing how the Vipr protein assembles along its guide RNA to form a helical filament, then binds DNA through a triplex structure — a mechanism distinct from how CRISPR operates.science+2

A Potentially More Powerful Tool

VIPR may hold practical advantages over CRISPR. It appears capable of targeting a broader range of genetic sequences, which could allow it to modify larger portions of the genome. The molecules involved are also smaller, which could make them easier to deliver into cells — a persistent challenge in gene therapy.nytimes

"The remarkably small size of VIPR positions these systems as transformative tools for genome engineering," said Kranusch, a microbiologist at Harvard Medical School who was not involved in the research.nytimes

What Comes Next

The discovery arrives at a moment of rapid expansion in the gene-editing field. Separate research published Thursday in Nature described new findings on how early human embryos repair DNA damage from editing tools, underscoring both the promise and the unresolved safety questions surrounding genetic modification. Meanwhile, Doudna's own lab has been active on multiple fronts, including the use of artificial intelligence to design synthetic CRISPR enzymes.technologynetworks+2

Whether VIPR will move from basic science into clinical or agricultural applications remains to be seen. The researchers demonstrated that the system can be reprogrammed for transcriptional repression in phages, but translating that capability into mammalian cells will require further work.biorxiv