Prime editor mediated correction of huntington’s disease CAG repeat mutation
Innovative gene editing approach using AAVdj-mediated dual prime editor to correct Huntington's Disease mutation with minimal off-target effects, validated in cell and animal models.
Overview
The University of Minnesota is pioneering a breakthrough gene editing technique to address Huntington's Disease (HD), a devastating neurodegenerative disorder caused by excess CAG repeats in the Huntingtin gene. This innovative approach utilizes an AAVdj-mediated delivery system of a dual prime editor to specifically correct the mutant Huntingtin allele. This method promises site-specific precision with off-target effects below detection limits, offering a potential therapeutic avenue to alter disease progression in HD patients.
Technical specifications
Key features:
- Utilizes AAVdj for efficient delivery of dual prime editors
- Employs a split-intein system to deliver improved prime editor (PE2*)
- Targets the mHtt gene with epegRNA and nicking sgRNA for precise editing
- Validation conducted in HEK293T cells and iPSC-derived cortical neurons
- Off-target analysis performed using PE-tag system
- Packaged in neurotrophic AAV-DJ8 serotype for targeted delivery
- Pilot in vivo study conducted in BACHD transgenic mouse model
Technology readiness level
This technology is currently at TRL 2, indicating that it is in the early experimental phase. Validation efforts are underway in both cellular models and animal studies to assess its efficacy and safety for future therapeutic applications.
About University of Minnesota
The University of Minnesota is a flagship, comprehensive public research university spanning multiple campuses, with a large research enterprise and clinical integration. Industry engages through co-located labs on the Twin Cities campuses, access to an academic health system for clinical translation, and pilot and field-testing facilities that speed scale-up. A statewide extension network and outreach centers provide real-world sites and data partnerships across Minnesota, while proximity to a dense medtech and Fortune 500 corridor enables frequent collaboration. Research is supported by competitive federal funding, including NIH, NSF, DOE, USDA, and DoD. A dedicated technology transfer office manages IP, licensing, sponsored research agreements, and startup incubation to speed commercialization.
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