Systemic delivery of microRNA for therapy of IBD

Research Project

Project/Area Number	16K15590
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	General surgery
Research Institution	Osaka University
Principal Investigator	Yamamoto Hiofumi 大阪大学, 医学系研究科, 教授 (30322184)
Project Period (FY)	2016-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000) Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	炎症性腸疾患 / マイクロRNA / 樹状細胞 / スーパーアパタイト / miR-29 / DDS / 核酸 / 全身デリバリー / 治療薬探索
Outline of Final Research Achievements	Although anti-TNF antibodies and immunosuppressive agents can achieve remission, recurrence is common in inflammatory bowel disease (IBD). Accordingly, novel therapeutic strategies are needed.The aim of this study was to establish microRNA-based therapy in an IBD model. For this purpose, we used microRNA-29 (miR-29) and a super carbonate apatite (sCA) nanoparticle as a drug delivery system. Injection of sCA-miR-29a-3p or -29b-3p into the tail veins of mice markedly prevented inflammation due to dextran sulfate sodium (DSS)-induced colitis. We found that sCA-negative control miR predominantly accumulated in CD11c+ dendritic cells (DCs) in the inflamed epithelium. RNA sequencing and Ingenuity Pathway Analysis revealed that miR-29a or -29b could inhibit interferon signaling pathways. Injection of sCA-miR-29b efficiently targeted CD11c+DCs in the inflamed mucosa. The present study showed that systemic delivery of miR-29 prevented DSS-induced colitis.