In two connected papers published in the journal Science last week, researchers from the Innovative Genomics Institute (IGI) lab of Jennifer Doudna described the surprising discovery of an ancient progenitor of CRISPR systems that had been overlooked because it uses a never-before-seen coding system to find and bind to DNA.
In nature, CRISPR is an adaptive immune system that bacteria and archaea use to fight viruses. CRISPR systems collect snippets of viral DNA, and they use matching pieces of RNA like mugshots to recognize invaders. The newly discovered system, named VIPR (Viral Interference Programmable Repeat), likely predates CRISPR and was instead found in viruses. The new studies rewrite CRISPR’s origin story with a surprising twist: bacteria appear to have stolen a weapon made by viruses to fight other viruses, and they turned it back on their enemy.
Unlike CRISPR, which pushes the two strands of DNA apart to find and cut the targeted DNA, VIPR takes a different approach that inspired its name: it twists itself around the DNA double helix like a snake.
VIPR has several advantages as a potential tool. First, it’s incredibly small — the smallest RNA-guided system that has been found. This makes it significantly easier to deliver into cells, often a challenge for the large CRISPR enzymes. VIPR also has no limitations on where it can target in a genome. CRISPR-Cas9 requires a short sequence called a “PAM” to be near the place where it binds and cuts DNA; VIPR can be reprogrammed to target anywhere in a genome.
“There’s no system that wraps around DNA like this. We suspect that this unusual geometry should allow for different kinds of applications people couldn’t do before,” said Peter Yoon, the study’s first author who performed his research in Jennifer Doudna’s lab as a molecular and cell biology graduate student.
The research team used AI tools to identify a list of proteins that could be related to CRISPR based on their shape. One of the top candidates was a strain that Doudna fortuitously had stored in her lab freezer.
