Development of non-invasive protein drug delivery system across the blood-brain barrier

• Project/Area Number: 23500547
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: KONDO Tetsuro 独立行政法人産業技術総合研究所, バイオメディカル研究部門, 主任研究員 (30344229)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 抗体医薬 / タンパク医薬 / 中枢神経系 / 血液脳関門 / 脳毛細血管内皮細胞 / アストロサイト / 指向性進化工学 / ファージディスプレイ / 薬物送達システム / 医薬分子設計 / 薬物輸送担体 / ドラッグデリバリー / バクテリアディスプレイ / ペプチド

Outline of Final Research Achievements

We have developed new technologies of directed evolution to engineer functional peptide motifs that interact with membrane proteins expressed on the blood-brain barrier (BBB), aiming at establishing non-invasive protein drug delivery to the central nervous system. Using an in vitro BBB model, we performed repetitive selection and amplification of random peptide libraries and obtained peptide motif candidates that characteristically interact with the plasma membranes of brain-derived microvascular endothelial cells.

Research Products

• [Journal Article] Random peptide library based on a spider neurotoxin, and utilization of the library in in-vitro evolution directed to GPCR ligands. (2012)
  • Author(s): Kubo T, et al.
  • Journal Title: Toxicon Volume: 60 Pages: 113-113
  • Peer Reviewed
• [Presentation] Development of the PERISS method to generate GPCR ligands/binders from a random peptide library with a spider neurotoxin scaffold (2012)
  • Author(s): Tai Kubo
  • Organizer: Biophysical Society 56th Annual Meeting
  • Place of Presentation: San Diego Convention Center, San Diego, USA
• [Presentation] In vitro evolution of peptide neurotoxins directed to receptor ligands (2): Application of a newly developed PERISS method to generate m2 muscarinic receptor ligands from a random peptides with an ICK motif (2011)
  • Author(s): Tai Kubo
  • Organizer: 9th Australian Peptide Conference
  • Place of Presentation: Conference Centre, Hamilton Isl., Australia