UC Berkeley researchers discover tiny CRISPR protein

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Lawrence Berkeley National Laboratory/File

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In a collaborative effort, a research team composed of scientists from UC Berkeley and the U.S. Department of Energy Joint Genome Institute discovered a CRISPR protein, Cas14, the smallest gene-editing tool known to date.

CRISPR operates by entering cells and modifying genetic code by replacing mutated genes with correct ones. Researchers think the small size of the Cas14 protein can be used to edit the genes in small cells and viruses to hopefully improve diagnostic systems.

“The key here is that they’re very small, and we use them for diagnostic applications. We’re able to treat this as a kind of diagnostic platform,” said Lucas Harrington, a co-author of the study and a campus graduate student.

Harrington collaborated with Jennifer Doudna, a campus professor of molecular biology and chemistry who discovered CRISPR. The researchers also worked with Jill Banfield, a campus professor of earth and planetary sciences and environmental science, policy and management.

Harrington said the small size of the newly discovered protein can help improve accuracy when looking to diagnose diseases such as cancer that begin with mutations in an individual’s DNA.

According to a campus press release, a strain of the Cas14 protein can be linked with a fluorescent marker. The protein then attaches to the intended DNA sequence, such as a cancer gene or an infectious bacteria, and begins to cut the DNA. Since the DNA is also paired with the marker, a fluorescent signal is produced.

“Your genome is this massive pool,” Harrington said, “What we’re looking for is a single change that’s usually an indicator for cancer or the difference between an infectious disease.”

According to the press release, Doudna adapted Cas14 to work with a diagnostic system called DETECTR. It uses two other CRISPR proteins, Cas12 and Cas13, to detect infectious organisms and genetic mutations. Harrington, Doudna and Janice Chen, who received her doctorate from UC Berkeley, helped co-found the company Mammoth Biosciences to commercialize the tool.

Researchers found the Cas14 protein through a technique called metagenomic sequencing, which involves taking samples directly from the natural environment, rather than developing them in a lab.

Isaac Witte, an undergraduate researcher studying music and molecular and cell biology, emphasized the importance of Cas14.

“The fact that it can be so specific will be advantageous for diagnostics technology,” Witte said. “The fact that we got anything out of it at all was really surprising.”

Harrington said the protein was so small that it was easy to overlook. The researchers, however, decided to investigate and were “shocked” when they learned the protein was a functional CRISPR system.

“That’s the Berkeley way for biological research — we ask fundamental questions about biology,” Harrington said. “We just want to understand how things work.”

Contact Ronit Sholkoff at [email protected] and follow her on Twitter at @RonitSholkoff.