Crispr-based fluorescent tagging in ipsc models for huntington's disease
A CRISPR-based platform enabling real-time visualization of HTT protein dynamics in iPSCs, accelerating AAV gene therapy assessments for Huntington's disease by overcoming detection limitations of traditional methods.
Overview
The CRISPR-based fluorescent tagging platform provides a breakthrough in visualizing pathogenic protein dynamics in patient-derived induced pluripotent stem cells (iPSCs). This technology enables real-time monitoring of endogenously expressed huntingtin (HTT) protein, crucial for evaluating the efficacy of AAV-based gene therapies targeting Huntington's disease and similar trinucleotide repeat disorders. By allowing direct observation of HTT protein behavior within a physiologically relevant model, it addresses the limitations of conventional detection methods and significantly reduces the time and cost of therapeutic assessments.
Technical specifications
- Fluorescent Tagging: Utilizes CRISPR to introduce EGFP tags at endogenous loci of HTT proteins in iPSCs, overcoming antibody limitations such as low specificity and high background noise.
- Gene Editing: Employs guide RNA targeting with Cas9 and a donor plasmid containing HTT exon1-EGFP for precise editing.
- Platform Components: Includes Sendai virus for iPSC reprogramming, electroporation for high-efficiency gene editing, and transplantation into mice to verify in vivo aggregation of tagged proteins.
- Applications: Supports the development and validation of AAV therapies for Huntington's disease by providing a robust model to monitor therapeutic responses and protein dynamics.
Technology readiness level
Currently at Technology Readiness Level 3, this platform has demonstrated proof-of-concept with successful in vitro differentiation and in vivo transplantation trials underway to create humanized HD mouse models.
About ipsbio
iPS Bio is a South Korean biotechnology company established in 2019 that focuses on providing innovative solutions for intractable neurological diseases using induced pluripotent stem cell (iPSC) technology. The company develops therapeutics, including iPSC-derived neural precursor cell therapies for conditions such as Huntington’s disease, stroke, and Alzheimer’s disease, as well as small molecule drug candidates. Its research integrates patient-derived iPSCs and AI technology to create advanced drug discovery and screening platforms. Furthermore, the company offers personalized services, such as its My iCell Bank for customized iPSC generation and banking, aimed at advancing precision regenerative medicine.
By leveraging these stem cell-based approaches, iPS Bio aims to address unmet medical needs by restoring lost neurons and providing neuroprotective effects. The company’s pipeline includes various programs in preclinical stages, with research supported by partnerships and various grants within the regenerative medicine sector. Through its commitment to patient-centered treatment innovation, iPS Bio seeks to improve quality of life and deliver novel therapeutic options for neurodegenerative disorders, supported by a leadership team with extensive experience in stem cell research and global scientific collaboration.
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