Development of biological regulation system with artificial peptide

• Project/Area Number: 17H06263
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Single-year Grants
• Research Field: Pharmaceutical Sciences and related fields
• Research Institution: University of the Ryukyus
• Principal Investigator: MATSUSHITA MASAYUKI 琉球大学, 医学(系)研究科(研究院), 教授 (30273965)
• Co-Investigator(Kenkyū-buntansha): 片桐 千秋 琉球大学, 医学(系)研究科(研究院), 助教 (00443664) ; 高松 岳矢 琉球大学, 医学(系)研究科(研究院), 助教 (90801431) ; 早川 朋子 琉球大学, 医学(系)研究科(研究院), 助教 (30420821)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000); Fiscal Year 2019: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2018: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2017: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
• Keywords: 細胞膜 / ペプチド / 神経疾患 / 細胞内除法伝達 / 血液脳関網 / 胎盤 / 抗体 / ペプチドライブラリー / 細胞膜通過 / 腫瘍 / 血液脳関門 / DDS / CPP

Outline of Final Research Achievements

We have developed a method for directly controlling the biological function by introducing a target molecule into a cell by binding such as a protein to a cell invasion peptide that invades the cell. Unlike the method using a virus, since the protein is directly introduced into cells, there is no side effect such due to DNA damage, and the application to stem cell regulation technology and medical application is rapidly spreading. However, since the intracellular invasion peptides developed all over the world invade all cell types, in this study, we studied peptides that can selectively invade target cells. We have investigated the therapeutic effects in disease models using cell type specific invasion peptides that have been developed so far and that can be transported only to the target cells, and have newly developed peptides that penetrate the blood-brain barrier.

Academic Significance and Societal Importance of the Research Achievements

健康社会の実現に向け、疾患の早期診断や副作用のない治療を推進するためには、疾患罹患細胞への的確な診断薬や治療薬物の送達が待望されている。各種の臓器や細胞に選択的に侵入する技術をペプチドを用いて創出したものであり、幅広い疾患診断・治療法の開発に応用可能な基盤技術になる。人工ペプチドを用いた診断・治療システムが確立されると、それに付随する診断用の化合物などの多種類のイメージング用プローブの開発や、細胞選択的侵入ペプチドを利用する新しい医療機器の開発に繋がることが期待される。また、本システムは各種臓器、細胞を標的とすることが可能であり、癌だけでなく他疾患や基礎研究への幅広い波及効果も期待できる。

Research Products

• [Journal Article] TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival (2019)
  • Author(s): Mittermeier L, Demirkhanyan L, Stadlbauer B, Breit A, Recordati C, Hilgendorff A, Matsushita M, Braun A, Simmons DG, Zakharian E, Gudermann T, Chubanov V
  • Journal Title: Proc Natl Acad Sci U S A Volume: 116 Issue: 10 Pages: 4706-4715
  • DOI: 10.1073/pnas.1810633116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Deletion of Long Isoform of Eukaryotic Elongation Factor 1Bδ Leads to Audiogenic Seizures and Aversive Stimulus-Induced Long-Lasting Activity Suppression in Mice (2018)
  • Author(s): Kaitsuka T, Kiyonari H, Shiraishi A, Tomizawa K, Matsushita M
  • Journal Title: Front Mol Neurosci Volume: 11 Pages: 1-13
  • Peer Reviewed / Open Access