2024-2025_総合研究院パンフレット(英文)
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33In addition to providing thermodynamic stability for double-stranded RNA (making it less likely to disassociate into single strands), Dab8 also protects it against degradation by nucleolytic enzymes. We have found Research and development on nucleic acid drugs has intensified in recent years, and drug delivery system (DDS) technology for delivering nucleic acid drugs efficiently to target organs has become indispensable. An siRNA nucleic acid drug consisting of 20 mers of double-stranded RNA generally has low cell membrane permeability and cannot be efficiently taken up by cells.Previously, we had developed an artificial cationic peptide, Dab8 (L-2,4-diaminobutyric acid octamer), that specifically recognizes and binds to the double-helix structure formed by double-stranded RNA.The structure of the artificial cationic peptide (Fol-Dab8)Delivery of siRNA specifically to pancreatic cancer cells by the use of Fol-Dab8that if we synthesize Fol-Dab8, a molecule consisting of folic acid conjugated to Dab8, and complex it with siRNA, that siRNA can be efficiently delivered to cells that have high expression of folate receptors, such as pancreatic cancer cells.When we conjugated Fol-Dab8 with the siRNA, which has an inhibitory effect on the growth of pancreatic cancer cells, and delivered it intravenously to a human pancreatic cancer-bearing model mouse, we observed effective accumulation in cancer cells and significant inhibition of cancer growth. This demonstrated greater effectiveness than standard therapies using cancer drugs.Our goal is to produce drugs that can cure intractable cancers using this platform technology.Selective Delivery of siRNA to Pancreatic CancerDevelopment of Nucleic Acid Drugs That Target Intractable Cancer:

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