[3S02e] 05. Genome Editing Technology and its Applications - Part 3

5:05 PM - 5:25 PM JST(8:05 AM - 8:25 AM UTC)

[3GET-15-KL] Advanced iPSC Genome Engineering: A Platform for Large-Scale Loss-of-Function and Multi-Gene Gain-of-Function Screens for Cell Therapy Optimization

○Yasunori Aizawa^1,2,3 (1. Institute of Science Tokyo (Japan), 2. Kanagawa Institute of Industrial Science and Technology (Japan), 3. Logomix Biotechnology, Inc. (USA))

Keywords:

iPSC engineering,human genome writing

Enhancing the functionality of human induced pluripotent stem cells (iPSCs) for regenerative medicine requires precise and extensive genomic manipulation beyond traditional methods. We recently established a robust genome engineering platform designed for high-throughput functional screening and cell optimization.Our platform overcomes the limitations of conventional CRISPR-based start-codon disruption by enabling large-scale entire-gene deletions, providing a definitive approach for loss-of-function (LOF) screening. Complementary to this, we have established a high-capacity gain-of-function (GOF) system capable of simultaneously knocking in up to 12 genes and ensuring their stable, long-term expression within the iPSC genome.By integrating these large-scale LOF and GOF capabilities, we can systematically redesign cellular pathways to enhance therapeutic properties such as hypoimmunogenicity and differentiation. We will present specific case studies where this platform was utilized to develop next-generation iPSC-derived cells with superior clinical potential. Our results demonstrate how large-scale genome manipulation can accelerate the transition from basic stem cell biology to sophisticated cell-based therapies.