Medical innovation using gene therapy of transcriptional factor STAT3 in septic multiple organ dysfunction

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03757
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Nagoya University
• Principal Investigator: Naoyuki Matsuda 名古屋大学, 医学系研究科, 教授 (50332466)
• Co-Investigator(Kenkyū-buntansha): 服部 裕一 北海道医療大学, その他, 客員教授 (50156361)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 敗血症 / 遺伝子治療 / STAT3 / 炎症性サイトカイン / IL-6 / JAK2

Outline of Final Research Achievements

In septic mouse model (CLP) by cecal ligation and puncture, JAK2 activity and STAT3 activity was increased in time series. Synthetic administration of double-stranded STAT3 decoy oligodeoxynucleotide (ODN) reduced organ damage in major organs including the lungs, liver, kidneys. STAT3 decoy ODN reduced the overproduction of inflammatory cytokines and chemokines in CLP mice, and significantly suppressed the production of inflammatory molecules such as HMGB1 in the lungs and liver. The result clarifies the role of STAT3 in sepsis and suggests the potential usefulness of STAT3 decoy ODN in gene therapy for sepsis.

Free Research Field

救急医学

Academic Significance and Societal Importance of the Research Achievements

敗血症は，さまざまな病気に合併し，臓器障害を進行させる病態である。本研究は，敗血症における転写因子STAT3の役割を，敗血症モデル動物の時系列で評価し，敗血症における遺伝子治療として転写因子STAT3をターゲットとした創薬科学の潜在的な有用性を示す結果となった。敗血症の新規治療薬として，IL-6受容体シグナルを制御することの提案となる学術的意義と，今後の創薬科学における社会的意義があると考えられた。