Development of adenovirus vector lacking VA RNA genes for efficient microRNA expression

2013 Fiscal Year Final Research Report

• Project/Area Number: 24701021
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Clinical oncology
• Research Institution: The University of Tokyo
• Principal Investigator: KONDO Saki 東京大学, 医科学研究所, 助教 (80451871)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: microRNA / ウイルスベクター / 遺伝子治療

Research Abstract

Non-coding small RNAs are involved in tumorigenesis. Although the transfection system is used to examine the role of small RNAs, it is not applicable for in vivo studies. Adenovirus vector (AdV) is used to deliver small RNAs including short-hairpin RNA (shRNA) and microRNA (miRNA). However, this vector expresses virus-associated RNAs (VA RNAs). Since VA RNAs are processed using the same pathway as shRNAs, a question arises as to whether VA RNAs influence the RNAi strategy when this vector is used. It has not been tested because VA-deleted AdVs have been difficult to develop.
We established a method for VA-deleted AdV production. We compared the activities of shRNAs against hepatitis C Virus (HCV) expressed from VA-deleted AdVs with conventional AdVs. The VA-deleted AdVs inhibited HCV production much more efficiently. Therefore, VA-deleted AdVs were more effective than the current AdVs for shRNA downregulation, probably because of no competition between VA RNAs and the shRNAs.

Research Products

• [Journal Article] Efficient production of adenovirus vector lacking genes of virus-associated RNAs that disturb cellular RNAi machinery (2013)
  • Author(s): Aya maekawa, Zheng Pei, Mariko Suzuki, Hiromitsu Fukuda, Yohei Ono, Saki Kondo, Izumu Saito and Yumi Kanegae
  • Journal Title: Scientific Reports Volume: 3巻
  • DOI: 10.1038/srep01136
  • Peer Reviewed
• [Journal Article] Adenovirus vectors lacking virus-associated RNAs expression enhance shRNA activity to suppress hepatitis C virus replication (2013)
  • Author(s): Zheng Pei, Guoli Shi, Saki Kondo, Masahiko Ito, Aya Maekawa, Mariko Suzuki, Izumu Saito, Tetsuro Suzuki and Yumi Kanegae
  • Journal Title: Scientific Reports Volume: 3巻
  • DOI: 10.1038/srep03575
  • Peer Reviewed
• [Presentation] (2013)
  • Author(s): 近藤小貴、前川文、裴崢、鈴木まりこ、斎藤泉、鐘ヶ江裕美
  • Organizer: 第19回日本遺伝子治療学会
  • Year and Date: 20130000
• [Presentation] (2013)
  • Author(s): 近藤小貴、斎藤泉、鐘ヶ江裕美
  • Organizer: 第72回日本癌学会
  • Year and Date: 20130000
• [Presentation] (2013)
  • Author(s): Saki Kondo, Aya Maekawa, Mariko Suzuki, Yumi Kanegae and Izumu Saito
  • Organizer: The 21th European Society of Gene and Cell Therapy collaborative Congress
  • Year and Date: 20130000
• [Presentation] (2013)
  • Author(s): 近藤小貴、前川文、裴崢、鈴木まりこ、鐘ヶ江裕美、斎藤泉
  • Organizer: 第61回日本ウイルス学会
  • Year and Date: 20130000
• [Presentation] (2013)
  • Author(s): 近藤小貴、前川文、裴崢、鈴木まりこ、鐘ヶ江裕美、斎藤泉
  • Organizer: 第36回日本分子生物学会
  • Year and Date: 20130000
• [Presentation] (2012)
  • Author(s): 近藤小貴、斎藤泉、Nic Jones
  • Organizer: 第18回日本遺伝子治療学会
  • Year and Date: 20120000
• [Presentation] (2012)
  • Author(s): 近藤小貴、鐘ヶ江裕美、斎藤泉
  • Organizer: 第17回日本癌学会
  • Year and Date: 20120000
• [Presentation] (2012)
  • Author(s): Saki Kondo, Yumi Kanegae, Nic Jones, Izumu Saito
  • Organizer: The 20th European Society of Gene and Cell Therapy meeting
  • Year and Date: 20120000
• [Book] 実はもっと簡単で使いやすいアデノウイルスベクター(第32巻) (2014)
  • Author(s): 近藤小貴, 他
  • Total Pages: 103-108
  • Publisher: 羊土社
• [Book] アデノウイルスベクターの最近の進展:VA欠失ベクターを中心に, 日本ウイルス学会 (第63巻) (2013)
  • Author(s): 近藤小貴, 他
  • Total Pages: 155-164