Oncolytic virus targeting oral cancer stem cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09737
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Hokkaido University
• Principal Investigator: YASUDA MOTOAKI 北海道大学, 歯学研究院, 准教授 (90239765)
• Co-Investigator(Kenkyū-buntansha): 東野 史裕 北海道大学, 歯学研究院, 准教授 (50301891)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: アデノウイルス / UTR

Outline of Final Research Achievements

All transcribed mRNAs, a minimum of 20 late viral RNAs, contain the common 5’UTR, which is called as Tripartite Leader, and this sequence is required for preferential translation of late viral proteins during late infection period. In the present study, we have demonstrated a novel role for E4 orf4 protein in the late adenoviral mRNA translation. Tripartite Leader tagged construct (TrLdr-LUC) transfected cells showed more than 10-fold higher luciferase activity compared with control transfectants, whereas no significant increase of luciferase mRNA amount was detected in TrLdr-LUC transfected cells. At least 2 folds increase of luciferase activities were observed, and the mutational analysis indicated that E4orf4, but not E4 orf3 or E4 orf6, was required for the enhanced translation. It is likely that E4 orf4 or OMB1 containing complex is involved in so-called Ribosome Shunt system.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

アデノウイルスは遺伝子治療研究の約２５％で使用されるベクターであるが、ほとんどの組み換えウイルスは自己複製不能で全てのがん細胞への導入は困難であり、また大量に感染させると肝臓に集積し副作用の原因となる。本研究で明らかとなったウイルス遺伝子翻訳システムの詳細は腫瘍溶解アデノウイルスをより効果的な手法とするのに有用である。また”がん幹細胞”における本翻訳システムの詳細についての解析は、さらに効果的な腫瘍会ウイルス作成への大きな一歩となる。