A Novel Viral Administration Method for Local ALS model and therapy: Pathology of TDP43 fragmentation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09532
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: University of the Ryukyus
• Principal Investigator: Kamizato Kota 琉球大学, 医学(系)研究科(研究院), 助教 (10554454)
• Co-Investigator(Kenkyū-buntansha): 垣花 学 琉球大学, 医学(系)研究科(研究院), 教授 (20274897)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 軟膜下投与

Outline of Final Research Achievements

1) Adeno-associated virus serotype virus with ubiquitin as promoter was generated for gene expression and protein expression experiments using cultured human neuroblastoma cells and primary mouse neural culture cells.And TDP-43 expression was confirmed.
2) As a preliminary experiment, we conducted an experiment to induce green fluorescent protein (GFP) by subchondral injection into the spinal cord of wild-type SD rats. Immunohistological examination confirmed strong expression of GFP.
Subchondral injection of AAV9-Syn-pTDP43 was performed for histological evaluation of protein expression and neuronal cell death. Neuronal cell death could not be confirmed in immunohistological examination.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

脊髄における新たな遺伝子導入技術である軟膜下投与法による遺伝子導入を試みた。我々のこれまでの研究と同様に確実な遺伝子導入を行うことが可能であった。さらに手術手技による神経障害を生じなかったことから、手技の安全性に関して確認することができた。確実な遺伝子治療のためにもターゲットとなる遺伝子の選定が重要であることが確認された。