Evaluation of Off-target Effects of Antisense Oligonucleotides

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860116
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Osaka University
• Principal Investigator: YOSHIDA Tokuyuki 大阪大学, 薬学研究科(研究院), 研究員 (00649387)
• Research Collaborator: INOUE Taskao ; SASAKI Kiyomi ; NAITO Yuki ; OBUKA Satoshi
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 核酸医薬品 / Gapmer型アンチセンス / オフターゲット効果

Outline of Final Research Achievements

RNA targeting oligonucleotide therapeutics, such as antisense oligonucleotides (ASO), carry the risk of causing unintended toxicities or side effects. One of the potential toxicities is hybridization-dependent off-target effects which are caused by Watson and Crick base-pairing to unintended RNAs. It is assumed that improvements in potency and cellular delivery arising from chemically modified nucleic acids could increase the risk of hybridization-dependent toxicities. However, it is unclear how ASO affect the expression of unintended RNAs, for example, mRNAs which are partially complementary to the ASO. To reveal this point, we performed microarray analysis using a human cell line and several ASO with gapmer design having 2′,4′-BNA. In this study, we reveal that the criteria for judgment of “off-target candidate genes” in in silico analysis, and the possible design of the methods for the evaluation of off-target effects of ASO.

Free Research Field

安全性学