Innovative development of DDS for microRNA therapeutics by an application of anti-PCSK9 antibody

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K14630
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: INAZAWA Johji 東京医科歯科大学, 難治疾患研究所, 教授 (30193551)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: がん / マイクロRNA / 核酸抗がん薬 / DDS / 脂質ナノ粒子 / PCSK9 / LDLR / LNP

Outline of Final Research Achievements

Tumor-suppressive microRNAs (TS-miRs) target multiple cancer-promoting genes concurrently and may be useful as a therapeutic agent for cancer therapy. The development of drug delivery system (DDS) is critical for the implementation of miR-based therapeutics. miR-X we identified effectively induces apoptosis by concurrently directly targeting multiple genes associated with cytoprotective mechanisms in esophageal cancer cells. In this project, we investigated therapeutic potential of the lipid-nanoparticle (LNP)-mediated DDS for miR-634-based cancer therapy. We confirmed the enforced expression of miR-X to be able to induce the apoptosis in various cancer cell lines. In xenograft tumors of BxPC3 cells, a pancreatic cancer cell line, in mice, the intravenous administration of the LNP incorporated miR-X significantly induced tumor growth inhibition. These results suggest therapeutic utility of LNP-mediated DDS for TS-miR(s) to cancer cells.

Free Research Field

分子腫瘍学