Collaborating Investigator: Seung-Woo Cho
Affiliation: Yonsei University, Korea

Funding Status: National Research Foundation (NRF) of Kore
Project Period: 03/01/17-02/28/20

Summary

Pluripotent reprogramming and direct lineage reprogramming hold tremendous potential as powerful strategies for providing alternative autologous cell sources for cell therapeutics and disease modelling. Target lineage cells can be derived from human induced pluripotent stem cells (hiPSCs) or directly converted from human fibroblasts for cell therapy and tissue engineering. Using cellular reprogramming technology, disease models of many human disorders can also be reconstructed to elucidate previously unknown pathogenic mechanisms of disease development and to test new therapeutic targets. Our project will focus on the establishment of novel methodologies enabling clinically-relevant neuronal differentiation of hiPSCs and neuronal direct reprogramming. Need for TR&D Technology: The goal of SP #3 is creation and use of nanobiotechnology to engineer stem cells. The BEAQ polymer libraries and high-throughput optimization approaches developed as part of TR&D2 for cellular engineering will be readily disseminated (push) to be utilized as enabling non-viral gene transfer technology for diverse regenerative medicine applications. This significantly amplifies the impact of this bioengineered technology. This SP demonstrates the broad utility of the innovative TR&D2 materials that will be developed for bioengineering.

Specific Aim 1: Utilize polymer nanoparticles for non-viral transfection of human induced pluripotent stem cells and reprogramming of human induced pluripotent stem cells to neurons.
Specific Aim 2: Utilize polymer nanoparticles for transfection of human fibroblasts for transdifferentiation into neurons.

A major practical challenge in cellular reprogramming technology is safe and efficient direction of hiPSC differentiation or human fibroblasts directly into desired lineages and preparation of highly mature, functional neurons required for clinical applications. In this project, the most efficient non-viral polymeric vectors will be identified from polymer libraries for hiPSC differentiation and direct reprogramming to generate functional neuronal cells with a high therapeutic potential both in vitro and in vivo.