CRISPR DNA modification has pros and cons, says U of U scientist
Jan 9, 2024, 2:00 PM
(Charlie Ehlert/University of Utah Health)
SALT LAKE CITY — CRISPR feels a little like evolutionary magic. Short for “clustered regularly interspaced short palindromic repeats”, it is a technology scientists use to target specific DNA in living organisms. CRISPR has its pros and cons, and Utah is at the forefront of its research.
But it’s not technology in the way we normally think of it. There are no bots or AI here. This technology was developed over millions of years by bacteria in its effort to fight off viruses. These bacteria developed immune systems against viruses. CRISPR co-ops the immune system and directs it to make changes in DNA.
“Our DNA has all the information we need to tell us how to build our body and make it work,” explained Dr. Randall Peterson, chemical biologist and Dean of the University of Utah’s College of Pharmacy. “It’s a very long book, and CRISPR is like programmable scissors we can use to say, ‘Out of the 3.3 billion letters in this book, we want you to cut precisely in this one area’.”
The CRISPR revolution: pros and cons in Utah
CRISPR has pros and cons, but a transformative effect on the way scientists like Peterson do their research. The early applications of CRISPR were used to remove mutations in DNA.
For example, the recently FDA-approved treatment of sickle cell anemia uses CRISPR in this way. Peterson explained that with sickle cell anemia, doctors take stem cells out of the patient’s body. They correct them in the lab and then put the corrected cells back in the patient.
“The cool thing about CRISPR research is it is opening up our minds to all kinds of possibilities that were not in the realm of imagination previously,” Peterson said. “There are new generations, including something called prime editing, which couples the cutting to a correction function. I think we’ll see new generations of CRISPR therapeutics in the future.”
One of the most common methods doctors use to insert CRISPR into a patient or lab subject is with a virus.
“You insert the components needed for the machinery of CRISPR into the virus,” Peterson explained. “Then, when the virus infects the cell, it injects these components into the cell. Viruses have evolved to inject their own DNA or RNA into a person’s cell to infect the cell. Now, we have tricks for co-opting the viruses and using them to introduce the CRISPR components.”
CRISPR research at the University of Utah
CRISPR is used most extensively in research.
“There are thousands of labs now around the world who are using CRISPR to try to understand genes and their functions,” Peterson said. “It’s spawned hundreds of derivative technologies, including in diagnostics.”
Peterson works a lot with zebrafish in his lab at the University of Utah.
“We and others had developed technologies for knocking out a single gene in a zebrafish to see what impact that gene had on the fish,” he said. “My lab has always been interested in doing big-scale experiments where we can test thousands of genes to see which might be contributing to a particular biological phenomenon.”
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University of Utah scientists have developed a technology called MIC-Drop, which stands for Multiplex Intermixed CRISPR droplets. It’s sort of like automation for genetic manipulation.
“Now we can knock out hundreds or even thousands of genes very efficiently and quickly to figure out what they’re doing. We can disrupt hundreds of genes all in parallel and see which of them is contributing to a particular disease or other phenomenon.”
Cons of CRISPR
Scientists and other thought leaders have expressed concern about CRISPR. You’ll remember years ago when a scientist in China named He Jiankui used CRISPR to edit the genome of two babies. He didn’t do it to make them smarter or taller or stronger. He did it to make the girls resistant to HIV infection, but it set off a firestorm of ethical questions.
“I think that it’s a legitimate worry,” Peterson said. “We need to start grappling with where the line is. We’re fixing a sickle cell disorder in a patient, and it’s not affecting their germline. It’s just making them better. That’s on one end of the spectrum. There is every possible iteration between that and controlling non-disease-related traits like height or hair color. I think most people recognize that one extreme is fine and the other extreme is not.”
Where will you go with CRISPR?
The research and application of CRISPR are growing every day. The global market for CRISPR-related technology products was $3.2 billion in 2022. It may reach $9.2 billion by 2027.
“My lab is really interested in building tools and technologies that will accelerate the pace of scientific research,” Dr. Peterson explained. “We don’t know what the functions are of thousands of genes. They are still mysterious to us.”
This is a fascinating time for scientists and clinicians.
“It is an exciting time to be thinking about the clinical impacts of this technology for all of us,” Peterson said.