Terminal bridging of siRNA duplex at the ribose 2′ position controls strand bias and target sequence preference
Small interfering RNA (siRNA) and short hairpin RNA (shRNA) are widely used as RNA interference (RNAi) reagents. Recently, truncated shRNAs that trigger RNAi in a Dicer-independent manner have been developed. We generated a novel class of RNAi reagent, designated enforced strand bias (ESB) RNA, in w...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-06-01
|
| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253123000999 |
| _version_ | 1797835684870881280 |
|---|---|
| author | Atsushi Shibata Hisao Shirohzu Yusuke Iwakami Tomoaki Abe Chisato Emura Eriko Aoki Tadaaki Ohgi |
| author_facet | Atsushi Shibata Hisao Shirohzu Yusuke Iwakami Tomoaki Abe Chisato Emura Eriko Aoki Tadaaki Ohgi |
| author_sort | Atsushi Shibata |
| collection | DOAJ |
| description | Small interfering RNA (siRNA) and short hairpin RNA (shRNA) are widely used as RNA interference (RNAi) reagents. Recently, truncated shRNAs that trigger RNAi in a Dicer-independent manner have been developed. We generated a novel class of RNAi reagent, designated enforced strand bias (ESB) RNA, in which an siRNA duplex was chemically bridged between the 3′ terminal overhang region of the guide strand and the 5′ terminal nucleotide of the passenger strand. ESB RNA, which is chemically bridged at the 2′ positions of ribose (2′-2′ ESB RNA), functions in a Dicer-independent manner and was highly effective at triggering RNAi without the passenger strand-derived off-target effect. In addition, the 2′-2′ ESB RNA exhibited a unique target sequence preference that differs from siRNA and silenced target sequences that could not be effectively suppressed by siRNA. Our results indicate that ESB RNA has the potential to be an effective RNAi reagent even when the target sequence is not suitable for siRNA. |
| first_indexed | 2024-04-09T14:57:34Z |
| format | Article |
| id | doaj.art-7fa797aaa0604488b979cd3b9dfb4ed7 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-09T14:57:34Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-7fa797aaa0604488b979cd3b9dfb4ed72023-05-02T04:05:03ZengElsevierMolecular Therapy: Nucleic Acids2162-25312023-06-0132468477Terminal bridging of siRNA duplex at the ribose 2′ position controls strand bias and target sequence preferenceAtsushi Shibata0Hisao Shirohzu1Yusuke Iwakami2Tomoaki Abe3Chisato Emura4Eriko Aoki5Tadaaki Ohgi6Division of R&D, Bonac Corporation, 1488-4 Aikawa, Kurume, Fukuoka 839-0861, Japan; Corresponding author Atsushi Shibata, Division of R&D, Bonac Corporation, 1488-4 Aikawa, Kurume, Fukuoka 839-0861, Japan.Division of R&D, Bonac Corporation, 1488-4 Aikawa, Kurume, Fukuoka 839-0861, Japan; Fukuoka Center for Disease Control and Prevention, Kurume, Fukuoka, JapanDivision of R&D, Bonac Corporation, 1488-4 Aikawa, Kurume, Fukuoka 839-0861, JapanDivision of R&D, Bonac Corporation, 1488-4 Aikawa, Kurume, Fukuoka 839-0861, JapanDivision of R&D, Bonac Corporation, 1488-4 Aikawa, Kurume, Fukuoka 839-0861, JapanDivision of R&D, Bonac Corporation, 1488-4 Aikawa, Kurume, Fukuoka 839-0861, JapanDivision of R&D, Bonac Corporation, 1488-4 Aikawa, Kurume, Fukuoka 839-0861, JapanSmall interfering RNA (siRNA) and short hairpin RNA (shRNA) are widely used as RNA interference (RNAi) reagents. Recently, truncated shRNAs that trigger RNAi in a Dicer-independent manner have been developed. We generated a novel class of RNAi reagent, designated enforced strand bias (ESB) RNA, in which an siRNA duplex was chemically bridged between the 3′ terminal overhang region of the guide strand and the 5′ terminal nucleotide of the passenger strand. ESB RNA, which is chemically bridged at the 2′ positions of ribose (2′-2′ ESB RNA), functions in a Dicer-independent manner and was highly effective at triggering RNAi without the passenger strand-derived off-target effect. In addition, the 2′-2′ ESB RNA exhibited a unique target sequence preference that differs from siRNA and silenced target sequences that could not be effectively suppressed by siRNA. Our results indicate that ESB RNA has the potential to be an effective RNAi reagent even when the target sequence is not suitable for siRNA.http://www.sciencedirect.com/science/article/pii/S2162253123000999MT: Oligonucleotides: Therapies and ApplicationsRNA interferencechemically bridged siRNAESB RNAstrand biasoff-target effect |
| spellingShingle | Atsushi Shibata Hisao Shirohzu Yusuke Iwakami Tomoaki Abe Chisato Emura Eriko Aoki Tadaaki Ohgi Terminal bridging of siRNA duplex at the ribose 2′ position controls strand bias and target sequence preference Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Therapies and Applications RNA interference chemically bridged siRNA ESB RNA strand bias off-target effect |
| title | Terminal bridging of siRNA duplex at the ribose 2′ position controls strand bias and target sequence preference |
| title_full | Terminal bridging of siRNA duplex at the ribose 2′ position controls strand bias and target sequence preference |
| title_fullStr | Terminal bridging of siRNA duplex at the ribose 2′ position controls strand bias and target sequence preference |
| title_full_unstemmed | Terminal bridging of siRNA duplex at the ribose 2′ position controls strand bias and target sequence preference |
| title_short | Terminal bridging of siRNA duplex at the ribose 2′ position controls strand bias and target sequence preference |
| title_sort | terminal bridging of sirna duplex at the ribose 2 position controls strand bias and target sequence preference |
| topic | MT: Oligonucleotides: Therapies and Applications RNA interference chemically bridged siRNA ESB RNA strand bias off-target effect |
| url | http://www.sciencedirect.com/science/article/pii/S2162253123000999 |
| work_keys_str_mv | AT atsushishibata terminalbridgingofsirnaduplexattheribose2positioncontrolsstrandbiasandtargetsequencepreference AT hisaoshirohzu terminalbridgingofsirnaduplexattheribose2positioncontrolsstrandbiasandtargetsequencepreference AT yusukeiwakami terminalbridgingofsirnaduplexattheribose2positioncontrolsstrandbiasandtargetsequencepreference AT tomoakiabe terminalbridgingofsirnaduplexattheribose2positioncontrolsstrandbiasandtargetsequencepreference AT chisatoemura terminalbridgingofsirnaduplexattheribose2positioncontrolsstrandbiasandtargetsequencepreference AT erikoaoki terminalbridgingofsirnaduplexattheribose2positioncontrolsstrandbiasandtargetsequencepreference AT tadaakiohgi terminalbridgingofsirnaduplexattheribose2positioncontrolsstrandbiasandtargetsequencepreference |