Allele-specific silencing of DYRK1A in iPSCs for Down syndrome treatment
This research explores allele-specific silencing of the DYRK1A gene in induced pluripotent stem cells (iPSCs) to treat neurodevelopmental and other phenotypes of Down syndrome (DS). The approach could correct gene expression, offering potential therapeutic benefits.
Overview
This innovative research focuses on allele-specific silencing of the DYRK1A gene in induced pluripotent stem cells (iPSCs) derived from individuals with Down syndrome (DS). The goal is to correct the overexpression of DYRK1A, a gene located on chromosome 21, which is implicated in various DS phenotypes such as neurodevelopmental defects and early onset Alzheimer's disease. By targeting this gene, the research aims to normalize cellular functions and mitigate DS-related abnormalities, offering a promising therapeutic pathway.
Technical specifications
- Utilizes Crispr/Cas9 gene editing to silence one allele of DYRK1A in trisomy 21 iPSCs.
- iPSCs are derived from monozygotic twins discordant for trisomy 21 to reduce genetic variability.
- The impact of DYRK1A silencing is assessed through differentiation into minibrain organoids, liver organoids, and hematopoietic progenitors.
- Analysis includes morphological and functional assessments, lineage marker expression, and transcriptome-wide RNA sequencing.
- Identification of DYRK1A targets through ChIP-Sequencing and phosphoprotein arrays.
Technology readiness level
This research is at Technology Readiness Level 3, indicating that the experimental concept has been proven in a laboratory environment. Further development and testing are required to advance towards clinical applications.
About Université de Fribourg
Université de Fribourg is a comprehensive public research university in Switzerland, with about 10,000 students and more than 2,000 researchers, combining broad academic scope with a personal, bilingual environment. Its urban campus in Fribourg and French-German operating context support cross-border collaboration and access to Switzerland’s central economic region. A dedicated Knowledge and Technology Transfer Service helps companies and researchers structure partnerships, negotiate contracts, protect intellectual property, and pursue start-up formation, including through Innosuisse and regional entrepreneurship support. Research is supported by competitive funding from the Swiss National Science Foundation, Innosuisse, the European Research Council, and European programmes.
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