International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Human Pluripotent Stem Cell-Derived Retinal Organoids: A Viable Platform for Investigating the Efficacy of Adeno-Associated Virus Gene Therapy

  • Hyeon-Jin Na (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jae-Eun Kwon (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Seung-Hyun Kim (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jiwon Ahn (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Ok-Seon Kwon (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kyung-Sook Chung (Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2023.05.24
  • Accepted : 2023.11.28
  • Published : 2024.05.30
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Abstract

With recent advances in adeno-associated virus (AAV)-based gene therapy, efficacy and toxicity screening have become essential for developing gene therapeutic drugs for retinal diseases. Retinal organoids from human pluripotent stem cells (hPSCs) offer a more accessible and reproducible human test platform for evaluating AAV-based gene therapy. In this study, hPSCs were differentiated into retinal organoids composed of various types of retinal cells. The transduction efficiencies of AAV2 and AAV8, which are widely used in clinical trials of inherited retinal diseases, were analyzed using retinal organoids. These results suggest that retinal organoids derived from hPSCs serve as suitable screening platforms owing to their diverse retinal cell types and similarity to the human retina. In summary, we propose an optimal stepwise protocol that includes the generation of retinal organoids and analysis of AAV transduction efficacy, providing a comprehensive approach for evaluating AAV-based gene therapy for retinal diseases.

Keywords

Acknowledgement

This research was supported by grants from Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program (KGM5362313), and the National Research Foundation of Korea (NRF-2022R1C1C1011202).

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