Development of Innovative Cancer Genome Editing Therapy Using Polymeric Micelles Implementing High Precision Intracellular Delivery Function

• Project/Area Number: 23H00546
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Cabral Horacio 東京大学, 大学院工学系研究科(工学部), 准教授 (10533911)
• Co-Investigator(Kenkyū-buntansha): 佐藤 守俊 東京大学, 大学院総合文化研究科, 教授 (00323501) ; 小嶋 基寛 国立研究開発法人国立がん研究センター, 先端医療開発センター, ユニット長 (30338470) ; 鈴木 利宙 国立研究開発法人国立がん研究センター, 先端医療開発センター, 研究員 (50530135) ; 持田 祐希 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 副主幹研究員 (60739134)
• Project Period (FY): 2023-04-01 – 2026-03-31
• Project Status: Granted (Fiscal Year 2024)
• Budget Amount: ¥46,800,000 (Direct Cost: ¥36,000,000、Indirect Cost: ¥10,800,000); Fiscal Year 2025: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000); Fiscal Year 2024: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000); Fiscal Year 2023: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
• Keywords: Gene editing / Cancer / KRAS / Cathepsin B / Endosome escape / polymeric micelles / Cas9

Outline of Research at the Start

The project involves synthesizing a suitable polymers for Cas9/sgRNA micelle formation and optimizing the parameters for release of Cas9/sgRNA for specific gene editing. The efficiency and specificity of the micelle-mediated delivery of Cas9/sgRNA will be evaluated in vitro and in vivo. The in vivo efficacy of the gene editing tool will be assessed by evaluating the antitumor activity after knocking out KRAS in xenografts and patient-derived xenograft models of colon and pancreatic cancer. Any potential side effects will be studies in mice.