UC Berkeley researchers discover smallest known gene-editing tool

Enzyme
Doudna Lab/Courtesy
UC Berkeley scientists uncovered the smallest known enzyme, dubbed CasΦ, which could transform gene editing and remove genetic diseases in human embryos.

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UC Berkeley scientists have uncovered the smallest enzyme yet, which could play a sizable role in modifying the human genome.

The enzyme, dubbed CasΦ, constitutes part of a CRISPR-Cas system, a gene-editing tool that leverages the immune systems of bacteria. Bacteria and viruses use proteins to target and slice the DNA of invaders or competitors. When these systems are transplanted into more complex organisms, it allows for the manipulation of DNA, a process with a broad range of applications, from removing genetic diseases in human embryos to modifying crops to better suit their environments.

The new enzyme, which is half the size of those previously used in CRISPR, is a valuable addition to the “ever expanding toolbox” of gene editing, according to study co-author and campus graduate student Connor Tsuchida. The enzyme’s small size allows it to be packaged into compact vectors for more precise targeting, added Patrick Pausch, study co-author and campus postdoctoral researcher.

The CasΦ enzyme also possesses a host of other unique features. Unlike the enzymes currently used, it is not found in humans. As a result, no one would have preexisting immunity to it, which would reduce the effectiveness of the gene editing.

According to Pausch, the enzyme also acts as a “multitasking enzyme” in that it guides itself to the targeted DNA rather than relying on other factors within the microorganism.

The study built upon work done during an earlier lab, which dealt with viruses containing CRISPR-Cas systems. The CRISPR-CasΦ system was extremely compact and lacked many of the genes found in other such systems, intriguing researchers.

“No one knew if those systems are actually functional CRISPR-Cas systems or if they are just some weird evolutionary intermediate stages of soon-to-be CRISPR-Cas systems,” Pausch said in an email. “Of course, we also wanted to see if this peculiar system can be used for genome editing.”

By targeting the disorder of the root, tools such as the CasΦ enzyme could allow human diseases to be treated with more effectiveness and accuracy than ever. The CasΦ enzyme has also been found to work well in plants, opening up avenues in agriculture, said Basem Al-Shayeb, study co-author and campus graduate student.

The researchers plan to gain a better understanding of the enzyme and the rules that govern its functionality. Only then, Tsuchida added, will they be able to develop and adapt vehicles to deliver CasΦ to particular cells or tissues within an organism.

“This is really still just the tip of the iceberg,” Tsuchida said in an email. “As we continue to delve into the arms race between viruses (phage) and bacteria we will continue to discover new defense systems like CasΦ.”

Contact Annika Rao at [email protected] and follow her on Twitter at @annikyr.