AI Article Synopsis
- The study highlights the potential of gene therapy for Huntington's disease (HD) by replacing harmful genetic mutations with normal sequences in genetically engineered pigs.
- A one-time injection of a virus carrying the Cas9 gene-editing tool and a guide targeting the mutant HTT gene led to a significant reduction of the mutated protein and improved neurological symptoms in the pigs.
- The results suggest that similar gene therapy approaches could be effective in treating not just HD, but other genetic neurodegenerative diseases as well.
Article Abstract
The monogenic nature of Huntington's disease (HD) and other neurodegenerative diseases caused by the expansion of glutamine-encoding CAG repeats makes them particularly amenable to gene therapy. Here we show the feasibility of replacing expanded CAG repeats in the mutant HTT allele with a normal CAG repeat in genetically engineered pigs mimicking the selective neurodegeneration seen in patients with HD. A single intracranial or intravenous injection of adeno-associated virus encoding for Cas9, a single-guide RNA targeting the HTT gene, and donor DNA containing the normal CAG repeat led to the depletion of mutant HTT in the animals and to substantial reductions in the dysregulated expression and neurotoxicity of mutant HTT and in neurological symptoms. Our findings support the further translational development of virally delivered Cas9-based gene therapies for the treatment of genetic neurodegenerative diseases.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41551-023-01007-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!