Nature子刊：体内碱基编辑，治疗亨廷顿病

TL;DR - A Nature Biomedical Engineering paper (July 29, 2026) from UIUC reports in vivo CRISPR base editing that disrupts the exon 13 splice acceptor site in the HTT gene, producing a proteolysis-resistant huntingtin isoform that eases Huntington's disease pathology in rodent models. It matters as a precision genome-editing route that blunts mutant HTT toxicity without ablating the essential full-length protein.

• Disease rationale: CAG-repeat expansion in HTT exon 1 yields mutant HTT; caspase-6 cleavage at Asp586 generates aggregation-prone N-terminal fragments driving neuronal loss. The caspase-6 consensus site spans exons 12–13, so skipping either exon removes it.
• Approach: the team screened 140+ base editor variants targeting HTT splicing elements and identified platforms that disrupt the exon 13 splice acceptor (SA), inducing exon skipping and a cleavage-resistant HTT isoform.
• In vivo results: delivery to the striatum of transgenic HD rodent models reduced HTT fragment formation and mHTT aggregation, lessened brain atrophy, and improved functional deficits.
• Positioning: unlike total HTT knockdown, this preserves full-length HTT needed for normal cell function; results are preclinical (rodent) only, with no clinical data reported.