Utah State University scientists recently unveiled a new type of CRISPR biotechnology with the ability to selectively target and shred the DNA of cancerous cells.
“The immune system of cave bacteria holds the cure for cancer," said Ryan Jackson, an associate professor of biochemistry at USU.
“Did I know that we were going to discover this?" Jackson continued. "Absolutely not, but I did know when I started working here at Utah State that bacterial immune systems could hold new biotech.”
He’s referring to a new breakthrough in biotechnology that he and his team discovered. It’s called Cas12a2 and it’s a type of CRISPR nuclease. But first off, what is CRISPR anyway?
“In nature, CRISPR is an immune system that bacteria have to fight against viruses," Jackson said. "It's pretty sophisticated, and it took researchers a little while to figure out exactly all the pieces of that immune system, but what they discovered is that there's a protein component, and then there's an RNA component.”
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. The name is complicated, but the idea is simple. Bacteria use CRISPR as part of their immune system. They keep genetic mugshots of viruses they’ve encountered before. If that virus shows up again, the CRISPR system helps the bacterium recognize it and send in a CRISPR-associated protein, or Cas protein, to attack.
For scientists, this system is useful because it can be programmed. Researchers can design a short piece of guide RNA, which works kind of like a molecular navigator, to match a chosen genetic sequence. That guide RNA pairs with a Cas protein, like Cas9, and together they search for the matching target. Once they find it, Cas9 cuts the DNA at the targeted spot. The actual edit comes later, when the cell repairs the cut, sometimes using instructions researchers provide.
“And what that means is that we now have a tool to cut DNA right where we want, and then you add that to other tools to fix that cut, and add or delete bases, and that gives you power to manipulate genetics," Jackson said.
Adding or deleting DNA base pairs means altering the rungs of the DNA helix — the genetic code that makes up an organism. CRISPR-Cas9 which was originally adapted for eukaryotic cells in 2012 and has since become a major tool in gene-editing research. Jackson’s new discovery is still a type of CRISPR nuclease, meaning it’s another type of Cas enzyme that cuts genetic material, but it does something a bit different.
“When it's activated, it goes on a DNA shredding rampage that kills the cell that's been infected and that saves the colony," Jackson said.
Jackson has been quoted by Utah State Today in calling the technology a holy grail in medicine.
“The holy grail term comes from the fact that if you think of any therapy, anytime you're trying to do any type of biotech, you want the ability to manipulate one thing, but not everything," Jackson said. "Many existing therapies don't do that. For example, in existing chemotherapy, you kill the cancer, but you also kill a bunch of healthy cells, and that's why you have such strong negative side effects.”
Remember, Jackson said that Cas12a2 could be an actual cure for cancer. And while that still needs a lot more work, the reason he’s excited is pretty clear.
“This is a tool we never had before, which could say, hey, based off of the genetics, I want to only kill this type of cell, but leave these other ones alone, and our data suggests that we have discovered that,” Jackson said.
Jackson’s colleagues have already tested Cas12a2 in a mouse model using human cancer cells. They placed patient-derived cancer cells into mice, then injected a Cas12a2 system designed to recognize RNA from those cancer cells.
When the system entered cancerous cells, it activated and killed them; when it entered surrounding tissue without that cancer RNA signal, it stayed off and was eventually broken down by the cell.
This is significant because cancer is notoriously difficult to target, since it arises within our own cells. What that means is that from the outside, they can look a lot like healthy cells. But that doesn’t matter for Cas12a2.
“We're not going off of what's on the outside, we're going off of what's on the inside, and what's on the inside is very different," Jackson said. "We're going after that genetic difference that makes it cancer.”
But that doesn’t mean there will be human cancer treatments in the next year. This new tool is incredible, but still quite young.
“Well, first of all, we have to do the work to show that it can work in primary tissue. So, everything in the paper is with what we'd call an immortalized cell line," Jackson said. "They're just a little bit removed from what would be going on in humans. So, getting tissue like real cancer straight from a patient. Does this kill those cells? Stem cells, can we kill stem cells if they have a mutation? We are doing that work right now.”
In fact, they’re already working with other researchers at the Huntsman Cancer Institute at University of Utah, but there’s still a long way to go before this technology sees any human trials.
Regardless, Jackson can't overstate how incredible this discovery is.
“I'm on the record for saying I thought I felt like I was on drugs. I was high. I mean, it was just like, oh my gosh, this could selectively kill cancer cells," Jackson said. "It was very euphoric, and my son has an autoimmune disease. It just opened up new possibilities.”
And those possibilities came from studying bacteria. Jackson and his team didn’t create Cas12a2 out of nothing. They discovered it in cave bacteria that someone else discovered. That’s basic research, foundational to science.
“If I was to downplay this discovery, I could say taxpayer money went to trying to figure out how cave bacteria fight viruses," Jackson said. "That sounds like a dumb use of taxpayer money, but on the flip side that investigation led to a new technology that could make cancer obsolete.”
Without basic research, Cas12a2 and many other breakthroughs would never exist. Ozempic has roots in Gila monster saliva. PCR, the technology behind COVID tests and modern genetics, came from bacteria in Yellowstone hot springs and glowing proteins from jellyfish transformed cell biology. And now, part of a future cancer therapy might have been hiding in cave bacteria the whole time.
