Overview
- Researchers at the University of Illinois reported in a Nature Biomedical Engineering paper that an in vivo CRISPR base‑editing approach reduced toxic huntingtin fragments and improved movement and neurodegeneration measures in mice, a result published July 29, 2026.
- The team designed base editors that disrupt the splice acceptor for HTT exon 13 so cells skip that exon and make proteolysis‑resistant huntingtin isoforms instead of turning the gene off.
- Investigators screened more than 140 base editors to pick candidates with strong on‑target activity and few unintended edits, then packaged lead editors into AAV and injected them into mouse brains to achieve the observed benefits.
- Authors say key next steps are to test the lead exon‑13 skipping editors in humanized mice and to assess tolerability, dose range, and target engagement in large animals while developing less invasive, nonviral delivery methods.
- The work is preclinical and funded mainly by the CHDI Foundation with NIH and foundation support, and it matters because preserving some wild‑type HTT may avoid risks of full gene inactivation while offering a new path toward therapies for people affected by Huntington’s disease.