Gene-editing tool CRISPR has helped create a new treatment for sickle cell disease, and other applications are being tested in numerous ongoing clinical trials. Yet scholars still did not know about its ancestral origins.
Earlier this month, multiple UC Berkeley researchers from professor Jennifer Doudna’s group at the Innovative Genomics Institute published their discovery of VIPR, a new genome editor found in viruses, which they hypothesize to be an ancestral predecessor of CRISPR.
In nature, both CRISPR and VIPR are actually defense systems within microorganisms, reading and remembering the genes of invading viruses.
Unlike CRISPR, VIPR doesn’t keep track of an entire sequence of genetic information, but only snippets, allowing it to recognize the same viruses even when they continue to mutate.
When utilized as a gene editing platform, VIPR could be key in targeting forms of cancer that quickly mutate, according to Kenneth Loi, a graduate student from Doudna’s group. Loi is a first author on the study, alongside former graduate student Peter Yoon.
“There are certain types of targets that mutate very rapidly, and in those cases you can imagine … they would eventually mutate away and prevent CRISPR from being able to recognize it,” Loi said. “In VIPR’s case, you can imagine if you target that same target site, it might be more robust to whatever mutations arise.”
VIPR’s potential wasn’t clear at the beginning of the project.
According to Loi, he and Yoon spent 14 months “banging (their) heads against the wall” before figuring out how to reprogram VIPR.
“It was very non-obvious what (VIPR) even does. All we could tell was that … it’s related (to CRISPR),” Loi said. “It was 14 months of just that, me and Peter working full time … when we finally cracked the code, it was electric.”
Researchers from other labs were recruited to assist with the project. Terry Zhang, a fellow graduate student in the Doudna Lab, and Trevor Docter, who was previously in molecular and cell biology professor Stephen Brohawn’s lab, joined the project to uncover the structure and biochemical mechanisms of VIPR. Their findings were published in another paper on the same day as Loi and Yoon’s paper announced the discovery of VIPR.
According to Yoon and Loi’s paper, this discovery suggests that there are more pathways for genome editing than previously thought. UC Berkeley professor Noah Whiteman, who utilizes CRISPR in his research reconstructing evolutionary pathways to understand biological traits, said he is interested in seeing if VIPR could enable longer and more easily programmable gene-editing than CRISPR.
“I’m sure very soon people are probably getting components of (VIPR) and trying to get it to work. So I would imagine very, very soon you’re going to see papers come out that implement (VIPR),” Whiteman said.