Development of RNA therapies for curing of type 1 diabetes

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H04530
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Juntendo University (2022-2023); Tokyo Medical and Dental University (2020-2021)
• Principal Investigator: Matsumto Masahito 順天堂大学, 大学院医学研究科, 特任教授 (90321819)
• Co-Investigator(Kenkyū-buntansha): 位高 啓史 東京医科歯科大学, 生体材料工学研究所, 教授 (60292926) ; 岡崎 康司 順天堂大学, 大学院医学研究科, 教授 (80280733)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 分化転換 / 1型糖尿病 / インスリン / 体細胞

Outline of Final Research Achievements

Type 1 diabetes mellitus is a serious glucose metabolism disease that results from the destruction of pancreatic beta cells localized in pancreatic islets, leading to insulin depletion and hyperglycemia, making insulin injections essential. Our technology of producing pancreatic beta cells by direct programming is a promising with ultra-high efficiency and high safety. This technology is expected to be clinically applicable not only to cell therapy but also to gene therapy. In this research project, it was observed that introduction of the reprogramming factor OKAP strongly induced insulin expression from somatic cells such as fibroblasts, etc. In vivo DR model mice, ectopic insulin-producing cell cells were significantly detected in organs other than the pancreas, demonstrating a potential novel technology.

Translated with DeepL.com (free version)

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

代表者らが発明したダイレクトリプログラミング(DR)による膵β細胞を含む人工膵島の作製手法は、幹細胞を介さないで体細胞へリプログラミング因子(OKAP)を導入すると、直接変換によって機能性膵β細胞(iβC)を約80%の効率で作出でき、さらに1型糖尿病モデルマウスの血糖改善効果を示すため、患者自身の体細胞を用いたex vivo細胞治療が可能である。さらに、mRNAを始めとする遺伝子治療開発に繋がり、従来の遺伝子・タンパク質補充療法とは異なり、患者体内において目的とする機能性インスリン産生細胞を作出できるため、画期的な次世代型の創薬モダリティとなり得る。