Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ymthe.2021.05.008
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dc.titleTargeting RNA Editing of Antizyme Inhibitor 1: a Potential Oligonucleotide-Based Antisense Therapy for Cancer.
dc.contributor.authorTai Tay, Daryl Jin
dc.contributor.authorSong, Yangyang
dc.contributor.authorPeng, Boya
dc.contributor.authorToh, Tan Boon
dc.contributor.authorHooi, Lissa
dc.contributor.authorKaixin Toh, Desiree-Faye
dc.contributor.authorHong, HuiQi
dc.contributor.authorTang, Sze Jing
dc.contributor.authorHan, Jian
dc.contributor.authorGan, Wei Liang
dc.contributor.authorMan Chan, Tim Hon
dc.contributor.authorKrishna, Manchugondanahalli S
dc.contributor.authorPatil, Kiran M
dc.contributor.authorMaraswami, Manikantha
dc.contributor.authorLoh, Teck Peng
dc.contributor.authorDan, Yock Young
dc.contributor.authorZhou, Lei
dc.contributor.authorBonney, Glenn Kunnath
dc.contributor.authorKah-Hoe Chow, Pierce
dc.contributor.authorChen, Gang
dc.contributor.authorKai-Hua Chow, Edward
dc.contributor.authorLe, Minh Tn
dc.contributor.authorChen, Leilei
dc.date.accessioned2021-06-23T07:53:32Z
dc.date.available2021-06-23T07:53:32Z
dc.date.issued2021-05-08
dc.identifier.citationTai Tay, Daryl Jin, Song, Yangyang, Peng, Boya, Toh, Tan Boon, Hooi, Lissa, Kaixin Toh, Desiree-Faye, Hong, HuiQi, Tang, Sze Jing, Han, Jian, Gan, Wei Liang, Man Chan, Tim Hon, Krishna, Manchugondanahalli S, Patil, Kiran M, Maraswami, Manikantha, Loh, Teck Peng, Dan, Yock Young, Zhou, Lei, Bonney, Glenn Kunnath, Kah-Hoe Chow, Pierce, Chen, Gang, Kai-Hua Chow, Edward, Le, Minh Tn, Chen, Leilei (2021-05-08). Targeting RNA Editing of Antizyme Inhibitor 1: a Potential Oligonucleotide-Based Antisense Therapy for Cancer.. Mol Ther. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ymthe.2021.05.008
dc.identifier.issn15250016
dc.identifier.issn15250024
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/192146
dc.description.abstractDysregulated adenosine-to-inosine (A-to-I) RNA editing is implicated in various cancers. However, no available RNA editing inhibitors have so far been developed to inhibit cancer-associated RNA editing events. Here we decipher the RNA secondary structure of antizyme inhibitor 1 (AZIN1), one of the best-studied A-to-I editing targets in cancer, by locating its editing site complementary sequence (ECS) at the 3'end of exon 12. Chemically modified antisense oligonucleotides (ASOs) which target the editing region of AZIN1 caused a substantial exon 11 skipping; while ECS-targeting ASOs effectively abolish AZIN1 editing without affecting splicing and translation. We demonstrate that complete 2'-O-methyl (2'-O-Me) sugar ring modification in combination with partial phosphorothioate (PS) backbone modification may be an optimal chemistry for editing inhibition. ASO3.2, which targets the ECS, specifically inhibits cancer cell viability in vitro and tumor incidence and growth in xenograft models. Our results demonstrate that this AZIN1-targeting, ASO-based therapeutics may be applicable to a wide range of tumor types.
dc.publisherElsevier BV
dc.sourceElements
dc.subjectA-to-I RNA editing
dc.subjectADAR1
dc.subjectAZIN1
dc.subjectCancer
dc.subjectRNA therapeutics
dc.subjectantisense oligonucleotides
dc.typeArticle
dc.date.updated2021-06-23T05:41:00Z
dc.contributor.departmentBIOMED INST FOR GLOBAL HEALTH RES & TECH
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF ANATOMY
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentLIFE SCIENCES INSTITUTE
dc.description.doi10.1016/j.ymthe.2021.05.008
dc.description.sourcetitleMol Ther
dc.published.statePublished
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