CHAMPAIGN, IL (Chambana Today) – A groundbreaking gene editing tool developed by researchers at the University of Illinois is showing promise in reducing the formation of amyloid-beta plaques, a hallmark of Alzheimer’s disease. This new technology, called SPLICER, is a major advancement in gene editing, offering a more efficient and precise way to address genetic diseases.

The innovative approach, led by Pablo Perez-Pinera, a professor of bioengineering at the University of Illinois, utilizes a gene editing technique known as exon skipping to selectively skip over genetic sections responsible for producing misfolded or toxic proteins, such as those involved in Alzheimer’s. This strategy has the potential to revolutionize treatments for a range of genetic disorders, including Huntington’s disease, Parkinson’s disease, and Duchenne’s muscular dystrophy.

Published in the prestigious journal Nature Communications, the study demonstrates the successful application of SPLICER in live mice, reducing the formation of amyloid-beta precursor proteins in the brain. These proteins, which accumulate into plaques, are central to the neurodegenerative process in Alzheimer’s, impairing cognitive function over time.

How SPLICER Works

SPLICER builds on the well-known CRISPR-Cas9 gene editing technology, but with significant improvements. Unlike CRISPR-Cas9, which requires a specific DNA sequence to target, SPLICER uses newer Cas9 enzymes that can bypass this requirement. This opens up new possibilities for editing genes that were previously difficult to target, such as those associated with Alzheimer’s.

The technique works by targeting exons, the coding sections of a gene that dictate how proteins are made. If one of these exons contains a mutation that leads to a toxic protein, SPLICER can “skip” that section, essentially allowing the body to bypass the problematic code and produce a healthier version of the protein. Think of it as skipping a bad page in a recipe book that would ruin the dish – instead, the recipe moves on to the next step.

“We’ve known for years that some genes have sections that cause problems,” explained Perez-Pinera. “With SPLICER, we can skip those problematic sections, leaving behind proteins that still function properly.”

Success in Mice Model

In their study, the researchers targeted a gene linked to Alzheimer’s and demonstrated that SPLICER could efficiently reduce the formation of amyloid-beta plaques in cultured neurons. In mice, the team observed a 25% reduction in the targeted exon associated with amyloid-beta, without any harmful off-target effects, a common concern in gene editing.

Another co-author, Shraddha Shirguppe, emphasized the improved efficiency of SPLICER compared to older methods. “Traditional exon-skipping techniques often leave part of the faulty exon intact, which can still produce undesirable effects. SPLICER skips the entire exon more effectively, ensuring that only the correct portions of the gene are expressed,” Shirguppe explained.

A Promising Future for Gene Therapy

While the potential of SPLICER is clear, Perez-Pinera cautioned that the technology is not a universal cure-all. “Exon skipping is a promising approach, but it only works if the resulting protein still functions properly,” he said. “For diseases like Alzheimer’s, Parkinson’s, and Duchenne’s muscular dystrophy, we believe this technique holds great promise. However, further research is needed to ensure safety and long-term efficacy before it can be used in human treatments.”

The next step for the team is to conduct long-term studies to assess the safety and potential side effects of SPLICER in animals. Perez-Pinera also stressed the importance of testing for any toxic effects that might arise from skipping certain gene sequences.

Support and Collaborations

This cutting-edge research was supported by various organizations, including the National Institutes of Health, the Muscular Dystrophy Association, the American Heart Association, and the Parkinson’s Disease Foundation. Perez-Pinera’s team also worked in collaboration with colleagues from the Carle Illinois College of Medicine and the Cancer Center at Illinois.

The discovery of SPLICER adds to the growing momentum in the field of gene therapy, where advancements in genetic editing are paving the way for new treatments for some of the most challenging diseases of our time. For patients suffering from neurodegenerative diseases like Alzheimer’s, the hope for a better, more effective treatment is growing stronger every day.