Researchers at the University of Illinois Urbana-Champaign have used a precise form of gene editing to ease Huntington’s disease in mice — not by switching off the culprit gene, but by changing how it is read.
Huntington’s is caused by an expanded stretch of CAG repeats in the HTT gene, which leads cells to produce a toxic, misfolded form of the huntingtin protein that damages neurons. Rather than silencing HTT entirely — which also does useful work — the team, led by Pablo Perez-Pinera and Thomas Gaj in the Department of Bioengineering, took a subtler route.
How it works
The researchers designed base editors — tools that rewrite a single DNA letter without cutting the double helix — to target exon 13 of HTT and disrupt a splice acceptor site. That prompts cells to skip the section encoding sites where the protein is cut into its most damaging fragments. “Instead of turning the protein off completely, we alter how the gene is read so that the most damaging protein fragments are not produced,” Gaj said. To find the best design, the team screened more than 140 base editors.
What happened in mice
Delivered into the brain using adeno-associated viruses (AAVs), the treated mice accumulated fewer toxic protein fragments, showed fewer symptoms, and had less brain degeneration than untreated animals. The work was published July 29, 2026 in Nature Biomedical Engineering.
The caveats
This is early, preclinical research: results in mice frequently fail to translate to people. The authors say the next steps are humanized mouse models and larger-animal studies to assess tolerability and define a safe, effective dosing window before any human testing could be considered.