◆Associate Professor Keisuke Taniuchi of the Department of Gastroenterology, Faculty of Medicine, is participating in a project to develop a therapeutic drug for intractable pancreatic cancer, which has been selected for the "Development of Drug Discovery Platform Technologies for Next-Generation Diagnostics" program by the Japan Agency for Medical Research and Development (AMED).
Release Date:
~Improving Delivery Efficiency and Stability: Aiming for a Breakthrough in Cancer Treatment with Next-Generation RNAi Therapeutics~
A research and development project titled “Research and Development of Innovative Next-Generation Nucleic Acid Therapeutics Using Folic Acid-Binding Cationic Peptides and siRNA,” in which Associate Professor Keisuke Tanai of the Department of Gastroenterology in the School of Medicine is participating, has been selected for the “Development of Drug Discovery Platform Technologies for Realizing Next-Generation Therapies and Diagnostics” program by the Japan Agency for Medical Research and Development (AMED). This project involves Lecturer Sato of Tokyo University of Science,Professor Wada, and others, and the "SNPD-siRNA (Single Nucleotide Polymorphism-Distinguishable siRNA)" method for designing siRNAs specific to single-nucleotide polymorphism (SNP) mRNA, developed by Specially Appointed Professor Cheng (formerly Associate Professor at the University of Tokyo) and others at Tokyo University of Science.
Nucleic acid therapeutics based on RNAi (RNA interference) are a promising drug development modality that has been the subject of vigorous research and development since the first product was launched in 2018. While siRNA (small interfering RNA), which is commonly used, consists of a double-stranded RNA molecule of approximately 20 base pairs, its low delivery efficiency to target organs has been a major challenge; in particular, delivering it to pancreatic cancer—a notoriously difficult-to-treat form of cancer—was considered extremely difficult.
Against this backdrop, Lecturer Sato andProfessor Wada and others at Tokyo University of Science have independently developed a novel cationic peptide called “Dab oligomer” that specifically binds to and stabilizes the helical structure formed by RNA/RNA double strands. Furthermore, through collaborative research with Associate Professor Keisuke Tanuchi, they have succeeded in enhancing the delivery of Dab oligomer to pancreatic cancer—where folate uptake is heightened—by incorporating folic acid into the Dab oligomer.
Associate Professor Taniuchi has discovered that siRNA can be delivered specifically to pancreatic cancer by administering a complex of fluorescently labeled siRNA and Fol-Dab8—a cationic peptide conjugated with folic acid—into the tail vein of mice bearing pancreatic cancer organoids.
In this joint research and development project, building on this innovative technology involving Dab oligomers and folate complexes,by combining it with "SNPD-siRNA," which specifically and highly accurately suppresses only single-base-mutated mRNA, we aim to develop next-generation nucleic acid therapeutics that deliver groundbreaking therapeutic effects while minimizing side effects, particularly for genetically mutated diseases such as pancreatic cancer—which is notoriously difficult to treat. Through this effort, we aim to bring new hope for treatment to patients suffering from various diseases, including pancreatic cancer, a particularly intractable form of cancer.
Research and Development Project Title: Pharmaceutical R&D Using Next-Generation Delivery Technologies / Establishment of Non-Clinical Testing and Manufacturing Methods for Development Candidates / Research and Development of Innovative Next-Generation Nucleic Acid Therapeutics Using Folic Acid-Conjugated Cationic Peptides and siRNA
Primary Target Disease: Pancreatic Cancer
Project Name: Development of Drug Discovery Platform Technologies for Next-Generation Therapy and Diagnostics (Pharmaceutical R&D Using Next-Generation Delivery Technologies / Non-clinical Testing of Development Candidates and Establishment of Manufacturing Methods)
Other participating institutions: Tokyo University of Science (lead institution), The University of Tokyo, Tokyo University of Science, Nihon University, Kanazawa University, Nippon Shokubai Co., Ltd., ANRis Co., Ltd.