Development of novel gene therapy system for genetic hematological disorders by using stealth RNA vector

2023 Fiscal Year Final Research Report

• Project/Area Number: 19H03613
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: University of Tsukuba
• Principal Investigator: Takada Hidetoshi 筑波大学, 医学医療系, 教授 (70294931)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 遺伝子治療 / 重症複合免疫不全症 / ステルス型RNAベクター

Outline of Final Research Achievements

We conducted gene therapy development research using stealth RNA vectors (SRV) for severe combined immunodeficiency. We have demonstrated that SRV can introduce genes into mouse hematopoietic stem cells/hematopoietic progenitor cells and CD34-positive cells derived from human umbilical cord blood efficiently. Differentiation of hematopoietic cells was confirmed by colony assay. When genes were introduced into common gamma chain-deficient cells using SRV, expression of the common gamma chain was achieved, and phosphorylation of STAT5 was confirmed upon stimulation with IL-2. Since it was sometimes difficult to maintain the proliferation of gene-transfected cells over a long period of time, we improved SRV and conducted a similar analysis. We will continue to improve SRV and apply it to other diseases.

Free Research Field

小児科学

Academic Significance and Societal Importance of the Research Achievements

海外では重症複合免疫不全症に対して、レトロウイルスやレンチウイルスなどのゲノム組み込み型ベクターを用いた遺伝子治療が行われている。しかしゲノム組み込み型ベクターでは、ゲノムの様々な部位にベクターが組み込まれることが大きな問題であり、実際に発がんなどの重大な副反応がおこっており、死亡例も報告されている。より安全なゲノム非組み込み型ベクターを用いた遺伝子治療開発研究が急務である。今回、改良型センダイウイルスベクター（ステルス型RNAベクター：略称SRV）を用いた遺伝子治療開発研究を行った。臨床応用に向けてSRVの改良を進める。