Crispr-based prevention of tandem-repeat expansions in huntington's disease
A novel CRISPR-mediated genome editing approach targets the Huntingtin gene to prevent somatic repeat instability in Huntington's disease. This method uses modified guide RNAs to block repeat expansions in patient-derived cell lines and humanized mouse models.
Overview
This innovative solution leverages CRISPR-mediated genome editing to prevent somatic repeat instability associated with Huntington's disease (HD). By targeting the Huntingtin gene (HTT) in patient-derived cell lines and humanized mouse models, this approach aims to block nucleotide tandem-repeat expansions. The use of modified guide RNAs enhances the stability of the DNA by preventing non-canonical secondary DNA structures, which are prone to damage and lead to repeat expansions. This solution is designed to maintain repeat length stability, offering a potential therapeutic strategy for HD and other tandem-repeat expansion diseases.
Technical specifications
- CRISPR-based genome editing: Targets the HTT gene in HD patient-derived induced pluripotent stem cells (iPSCs) and neuronal stem cells.
- Modified guide RNAs: Incorporate chemical modifications to prevent non-B-DNA formation and repeat expansions.
- In vitro and in vivo validation: Tested in iPSC lines and humanized mouse models for HD.
- Previous experience: Utilized in base-editing and CRISPR-Cas gene editing for X-linked agammaglobulinemia and CNS oligonucleotide introduction.
Technology readiness level
The technology is currently at TRL 4, indicating that the approach has been validated in a laboratory setting with experimental models. Future development aims to extend this method to additional tandem-repeat expansion disorders.
About Karolinska Institute
Karolinska Institutet is a health‑sciences–focused public medical university in the Stockholm region, known for translational research and clinical education. Its integration with Karolinska University Hospital enables access to large patient populations, biobanks, and end‑to‑end clinical trial capability. Industry partners engage through co‑located core facilities, contract research, and co‑development models supported by specialized laboratories and national research infrastructures. Research is backed by competitive funding from the Swedish Research Council, Vinnova, and European Union frameworks. A dedicated technology transfer office and incubator provide IP management, licensing, and venture creation, connecting companies with talent and facilities across the regional science park.
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