Gene editing tool could treat Alzheimer’s disease: U of I scientists


SOURCE: WCIA.COM
DEC 26, 2024

by: Molly Sweeney

Posted: Dec 26, 2024

CHAMPAIGN, Ill. (WCIA) — Researchers at the University of Illinois have found that a gene editing tool allows them to “skip” genes that lead to diseases, such as Alzheimer’s, in a mouse model.

The tool, called SPLICER, is more efficient than current gene editing tech and has a potential application in other diseases, according to the U of I News Bureau.

Pablo Perez-Pinera, professor of bioengineering, led the project.

U of I study tracks harmful particles in landfills, wastewater plants

“DNA contains the instructions to build everything that is responsible for how cells function. So, it’s like a book of recipes that contains very detailed instructions for cooking,” Perez-Pinera said. “But there are large regions of DNA that don’t code for anything. It’s like, you start the recipe for a turkey dinner, and then you hit a note that says, ‘continued on page 10.’ After page 10, it’s ‘continued on page 25.’ The pages between are gibberish.

Perez-Pinera wondered, what if there was a typo in the recipe page that made a meal inedible, or poisonous?

“If we cannot correct the typo directly, we could amend the note before it to send you to the next page, skipping over the page with the error, so that at the end you could make an edible turkey,” Perez-Pinera said. “Though you might lose out on the gravy that was on the skipped page, you’d still have dinner. In the same way, if we can skip the piece of the gene with the toxic mutation, the resulting protein could still have enough function to perform its critical roles.”

U of I team creates global warming resilient potatoes

SPLICER builds on the existing technology. It no longer needs a specific DNA sequence to latch onto, which opens up new targets like Alzheimer’s-related genes.

“Another problem we address in our work is precision in what gets skipped,” graduate student Angelo Miskalis, a co-first author of the paper, said. “With current exon-skipping techniques, sometimes not all of the exon gets skipped, so there’s still part of the sequence we don’t want expressed. In the cookbook analogy, it’s like trying to skip a page, but the new page starts in the middle of a sentence, and now the recipe doesn’t make sense. We wanted to prevent that.”

SPLICER targets an exon’s two key sequences making it more efficient. When targeting the Alzheimer’s gene, the researchers specifically coded for a sequence that eventually forms plaques on neurons in the brain as the disease progresses.

When the researchers analyzed their data, they found that the targeted exon was reduced by 25% in the SPLICER-treated mice.

U of I researchers work to develop breast cancer treatment

“When we originally tried to target this exon with older techniques, it didn’t work,” graduate student Shraddha Shirguppe, also a co-first author of the study, said. “Combining the newer base editors with dual splice editing skipped the exon at a much better rate than we were previously able to with any of the available methods. We were able to show that not only could it skip the whole exon better, it reduced the protein that produces the plaque in these cells.”

Perez-Pinera said exon skipping may not be the solution for every disease, but it has the potential to be a game changer for several.

“Exon skipping only works if the resulting protein is still functional, so it can’t treat every disease with a genetic basis. That’s the overall limitation of the approach,” Perez-Pinera said. “But for diseases like Alzheimer’s, Parkinson’s, Huntington’s or Duchenne’s muscular dystrophy, this approach holds a lot of potential. The immediate next step is to look at the safety of removing the targeted exons in these diseases, and make sure we aren’t creating a new protein that is toxic or missing a key function. We would also need to do longer term animal studies and see if the disease progresses over time.”