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Around the turn of the century, microbiologists at Danisco USA Inc. had a problem: The bacteria they used to make yogurt and were getting infected with viruses. Investigating more deeply, the scientists found that some bacteria to fight off such viral invaders.

Scientists can use natural tools known as CRISPR-Cas systems to break, edit or add genes to organisms, now including people.

These virus-resistant bacteria carried weird, repetitive collections of DNA letters in their chromosomes — bits of DNA from their encounters with past viruses that the microbes had “saved” in their own genomes. It was a form of molecular memory akin to the way that remembers invaders so it can make antibodies against a recurring infection.

In this case, the microbes’ dubbed CRISPR-Cas, or more casually, just CRISPR, shreds any viral genome that matches the sequences in their molecular memory banks.

The yogurt-makers weren’t looking for biotechnology’s Next Big Tool. They just wanted to preserve the products in their vats. But other scientists soon realized the potential value of CRISPR : With some modifications, CRISPR allowed them to cut any genetic sequence they wanted to, greatly easing the challenge of genetic engineering.

CRISPR systems have taken the biotechnology world by storm, and kicking off a . In December 2023, the US Food and Drug Administration approved the first CRISPR-based gene-changing treatment: a new gene therapy for the excruciatingly painful blood disorder sickle cell anemia.

“It’s been revolutionary for research,” says Kevin Esvelt, an evolutionary engineer at the MIT Media Lab in Cambridge, Massachusetts. “It’s accelerating all of biotech.”

Traditional gene therapy was tested in the late 20th century, but toxicity and cancer were major setbacks. CRISPR systems were first discovered in bacteria and the technology has now been successfully incorporated into human gene therapy.

Ever since scientists discovered CRISPR, there’s been a nagging question: Do similar gene-altering systems also occur in animals, plants and fungi — life forms known as eukaryotes, defined by the nucleus in which they store their genetic material?

The answer, now, is a definitive yes, in the journal Nature, authored by molecular biologist Feng Zhang and colleagues at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts. The team found CRISPR-like DNA-snippers called Fanzors in an odd menagerie of eukaryotic critters, including fungi, algae, amoebae and a clam called the northern quahog (pronounced coe-hog).

Researchers hailed the finding as a fascinating addition to the CRISPR family tree. And the discovery raises more questions: What are Fanzors up to? Can they, too, make a splash in biotechnology? And might Fanzor and CRISPR be the tip of an iceberg’s worth of DNA-slicing systems awaiting discovery?

Here’s some of what we know about microbial CRISPR systems and the Fanzors-come-lately.

What is CRISPR?

Just cutting DNA to bits isn’t a big deal. The special trick that CRISPR systems add is to make those cuts only in precise, targeted spots. This requires two elements: One is a guide to that location, a short piece of RNA that matches the target DNA sequence. The other is a protein, an enzyme to act as the “scissors.” Microbes have evolved a handful of scissor enzymes that make this cut, with names like Cas9 and Cas12.

When microbes are infected by viruses, the microbes collect small pieces of the viral genetic sequences and stow them together in a segment of their genome called CRISPR repeats. The next time that virus comes along, the microbe can use those sequences to create the guide RNAs. It can then use the enzyme scissors to snip up the genetic material of the virus and defend itself.

About half of known bacteria, as well as most of other microbes known as archaea, have CRISPR-Cas systems. Bizarrely, even some viruses have , to fight back against microbes. So until the new study, eukaryotes were the only group totally left out of the fun.

In CRISPR-Cas gene editing, the Cas9 enzyme uses associated pieces of RNA to bind to a portion of the DNA genome. The enzyme then breaks both strands of DNA. The cell repairs this break — either imperfectly, creating a broken gene (left), or using a provided DNA template, resulting in a controlled change (right).

What does CRISPR offer biotechnology?

Every living organism uses the same basic DNA code and proteins, so the CRISPR-Cas system can theoretically work in any organism scientists drop it into — though in reality, some tweaking is generally required.

The simplest application is to cut out undesirable DNA. Once the Cas enzyme cuts a target gene, the cell will glue the DNA back together, but imperfectly, creating a broken gene. For some applications, breaking a gen