Citation: Huiping Shi, Shaojun Peng, Minghui Yang, Yuanyu Huang. Engineering circular RNA with Tetrahymena group Ⅰ intron ribozyme[J]. Chinese Chemical Letters, ;2025, 36(9): 111160. doi: 10.1016/j.cclet.2025.111160 shu

Engineering circular RNA with Tetrahymena group Ⅰ intron ribozyme

Huiping Shi ^a ,
Shaojun Peng ^b ,
Minghui Yang ^{a, b} ,
Yuanyu Huang ^{a, b, *,}

a.
School of Life Science, School of Interdisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology (BIT), Beijing 100081, China
b.
School of Interdisciplinary Science, Beijing Institute of Technology (BIT), Zhuhai 519088, China

yyhuang@bit.edu.cn

Received Date: 4 January 2025
Revised Date: 25 March 2025
Accepted Date: 28 March 2025
Available Online: 30 March 2025

Figures(3)

Linear mRNA vaccines are constrained by exonuclease susceptibility and instability, leading to compromised antigen expression. Circular RNA (circRNA) lacking canonical 5′ and 3′ untranslated regions demonstrates intrinsic exonuclease resistance. Current circularization strategies face three principal limitations: chemical methods produce non-native 2′, 5′-phosphodiester bonds; ribozyme-mediated approaches are restricted to RNA fragments shorter than 500 nucleotides; the Anabaena Group Ⅰ intron system retains immunogenic exon sequences. In contrast, the self-splicing Group Ⅰ intron ribozyme from Tetrahymena enables precisely controlled circularization through autonomous structural rearrangement, yielding exon-free constructs. Through optimized purification protocols, historical scalability challenges are systematically addressed. This Perspective establishes the mechanistic rationale and therapeutic superiority of this engineered RNA circularization platform.
- Circular RNA,
- Chemical methods,
- Group Ⅰ intron,
- Ribozyme,
- Tetrahymena
1. [1]
  M.J. Zhang, A. Hussain, B. Hu, et al., Nat. Commun. 15 (2024) 6463. doi: 10.1038/s41467-024-50752-9
2. [2]
  X.J. Chen, Y. Lu, Front. Bioeng. Biotechnol. 9 (2021) 787881. doi: 10.3389/fbioe.2021.787881
3. [3]
  C.X. Liu, S.K. Guo, F. Nan, et al., Mol. Cell. 82 (2022) 420–434 e426. doi: 10.1016/j.molcel.2021.11.019
4. [4]
  Z.Y. Ye, L.S. Li, L. Yang, et al., Exploration 4 (2024) 20230138. doi: 10.1002/EXP.20230138
5. [5]
  S. Khalid, M. Bilal, N. Rasool, M. Imran, Chin. Chem. Lett. 35 (2024) 109498. doi: 10.1016/j.cclet.2024.109498
6. [6]
  Y.J. Li, Y.N. Wang, Y.G. Luo, et al., Chin. Chem. Lett. 35 (2024) 109576. doi: 10.1016/j.cclet.2024.109576
7. [7]
  S. Petkovic, S. Müller, Nucleic Acids Res. 43 (2015) 2454–2465. doi: 10.1093/nar/gkv045
8. [8]
  Y.J. Dang, Y.R. Feng, X. Chen, et al., Chin. Chem. Lett. 35 (2024) 109660. doi: 10.1016/j.cclet.2024.109660
9. [9]
  B. Hu, B. Li, K. Li, et al., Sci. Adv. 8 (2022) eabm1418. doi: 10.1126/sciadv.abm1418
10. [10]
  Y.J. Li, J.Y. Li, Y.Q. Chang, Y.F. Lin, L. Sui, Chin. Chem. Lett. 35 (2024) 109414. doi: 10.1016/j.cclet.2023.109414
11. [11]
  N.G. Dolinnaya, N.I. Sokolova, D.T. Ashirbekova, Z.A. Shabarova, Nucleic Acids Res. 19 (1991) 3067–3072. doi: 10.1093/nar/19.11.3067
12. [12]
  N.I. Sokolova, D.T. Ashirbekova, N.G. Dolinnaya, Z.A. Shabarova, FEBS Lett. 232 (1988) 153–155. doi: 10.1016/0014-5793(88)80406-X
13. [13]
  N.G. Dolinnaya, M. Blumenfeld, I.N. Merenkova, et al., Nucleic Acids Res. 21 (1993) 5403–5407. doi: 10.1093/nar/21.23.5403
14. [14]
  T.E. England, O.C. Uhlenbeck, Biochemstry 17 (1978) 2069–2076. doi: 10.1021/bi00604a008
15. [15]
  C.K. Ho, S. Shuman, Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 12709–12714. doi: 10.1073/pnas.192184699
16. [16]
  G. Kaufmann, T. Klein, U.Z. Littauer, FEBS Lett. 46 (1974) 271–275. doi: 10.1016/0014-5793(74)80385-6
17. [17]
  R. Silber, V.G. Malathi, J. Hurwitz, Proc. Natl. Acad. Sci. U. S. A. 69 (1972) 3009–3013. doi: 10.1073/pnas.69.10.3009
18. [18]
  S. Yin, C.K. Ho, E.S. Miller, S. Shuman, Virology 319 (2004) 141–151. doi: 10.1016/j.virol.2003.10.037
19. [19]
  E. Ford, J.M. Ares, Proc. Natl. Acad. Sci. U. S. A. 91 (1994) 3117–3121. doi: 10.1073/pnas.91.8.3117
20. [20]
  K.A. Jarrell, Proc. Natl. Acad. Sci. U. S. A. 90 (1993) 8624–8627. doi: 10.1073/pnas.90.18.8624
21. [21]
  S. Mikheeva, M. Hakim Zargar, D. Carlson, K. Jarrell, Nucleic Acids Res. 25 (1997) 5085–5094. doi: 10.1093/nar/25.24.5085
22. [22]
  M. Puttaraju, M.D. Been, Nucleic Acids Res. 20 (1992) 5357–5364. doi: 10.1093/nar/20.20.5357
23. [23]
  R.A. Wesselhoeft, P.S. Kowalski, D.G. Anderson, Nat. Commun. 9 (2018) 2629. doi: 10.1038/s41467-018-05096-6
24. [24]
  R.A. Wesselhoeft, P.S. Kowalski, F.C. Parker-Hale, et al., Mol. Cell. 74 (2019) 508–520. e504. doi: 10.1016/j.molcel.2019.02.015
25. [25]
  A. Dallas, S.V. Balatskaya, T.C. Kuo, et al., Nucleic Acids Res. 36 (2008) 6752–6766. doi: 10.1093/nar/gkn637
26. [26]
  P.A. Feldstein, G. Bruening, Nucleic Acids Res. 21 (1993) 1991–1998. doi: 10.1093/nar/21.8.1991
27. [27]
  S.A. Kazakov, S.V. Balatskaya, B.H. Johnston, RNA 12 (2006) 446–456. doi: 10.1261/rna.2123506
28. [28]
  K.H. Lee, S. Kim, J. Song, et al., Mol. Ther. Nucleic Acids. 33 (2023) 587–598. doi: 10.1016/j.omtn.2023.07.034
29. [29]
  J.M. Burke, M. Belfort, T.R. Cech, et al., Nucleic Acids Res. 15 (1987) 7217–7221. doi: 10.1093/nar/15.18.7217
30. [30]
  L.X. Xu, Z.X. Shao, X. Fang, et al., Exploration 5 (2024) 20231065.
31. [31]
  P.P. De Deyn, R. D'Hooge, L.F.M. van Zutphen, Neurosci. Res. Commun. 26 (2000) 141–148. doi: 10.1002/1520-6769(200005/06)26:3<141::AID-NRC2>3.0.CO;2-V
32. [32]
  X. Liu, Y. Zhang, S.R. Zhou, et al., J. Control. Release 348 (2022) 84–94. doi: 10.1016/j.jconrel.2022.05.043
1. [1]
  Jian Li , Jinjin Chen , Qi-Long Hu , Zhen Wang , Xiao-Feng Xiong . Recent progress of chemical methods for lysine site-selective modification of peptides and proteins. Chinese Chemical Letters, 2025, 36(5): 110126-. doi: 10.1016/j.cclet.2024.110126
2. [2]
  Shiyu Hou , Maolin Sun , Liming Cao , Chaoming Liang , Jiaxin Yang , Xinggui Zhou , Jinxing Ye , Ruihua Cheng . Computational fluid dynamics simulation and experimental study on mixing performance of a three-dimensional circular cyclone-type microreactor. Chinese Chemical Letters, 2024, 35(4): 108761-. doi: 10.1016/j.cclet.2023.108761
3. [3]
  Mei Peng , Wei-Min He . Photochemical synthesis and group transfer reactions of azoxy compounds. Chinese Chemical Letters, 2024, 35(8): 109899-. doi: 10.1016/j.cclet.2024.109899
4. [4]
  Lihua HUANG , Jian HUA . Denitration performance of HoCeMn/TiO₂ catalysts prepared by co-precipitation and impregnation methods. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 629-645. doi: 10.11862/CJIC.20230315
5. [5]
  Zixuan Zhu , Xianjin Shi , Yongfang Rao , Yu Huang . Recent progress of MgO-based materials in CO₂ adsorption and conversion: Modification methods, reaction condition, and CO₂ hydrogenation. Chinese Chemical Letters, 2024, 35(5): 108954-. doi: 10.1016/j.cclet.2023.108954
6. [6]
  Jun Xiong , Ke-Ke Chen , Neng-Bin Xie , Wei Chen , Wen-Xuan Shao , Tong-Tong Ji , Si-Yu Yu , Yu-Qi Feng , Bi-Feng Yuan . Demethylase-assisted site-specific detection of N¹-methyladenosine in RNA. Chinese Chemical Letters, 2024, 35(5): 108953-. doi: 10.1016/j.cclet.2023.108953
7. [7]
  Tian Feng , Yun-Ling Gao , Di Hu , Ke-Yu Yuan , Shu-Yi Gu , Yao-Hua Gu , Si-Yu Yu , Jun Xiong , Yu-Qi Feng , Jie Wang , Bi-Feng Yuan . Chronic sleep deprivation induces alterations in DNA and RNA modifications by liquid chromatography-mass spectrometry analysis. Chinese Chemical Letters, 2024, 35(8): 109259-. doi: 10.1016/j.cclet.2023.109259
8. [8]
  Yan Liu , Yang Wang , Jiayi Zhu , Xuxian Su , Xudong Lin , Liang Xu , Xiwen Xing . Employing pH-responsive RNA triplex to control CRISPR/Cas9-mediated gene manipulation in mammalian cells. Chinese Chemical Letters, 2024, 35(9): 109427-. doi: 10.1016/j.cclet.2023.109427
9. [9]
  Keqiang Shi , Xiujuan Hong , Dongyan Xu , Tao Pan , Huiwen Wang , Hongru Feng , Cheng Guo , Yuanjiang Pan . Analysis of RNA modifications in peripheral white blood cells from breast cancer patients by mass spectrometry. Chinese Chemical Letters, 2025, 36(3): 110079-. doi: 10.1016/j.cclet.2024.110079
10. [10]
  Hyoseok Kim , Changyi Cui , Kohei Toh , Genyir Ado , Tetsuya Ogawa , Yixin Zhang , Shin-ichi Sato , Yong-Beom Lim , Hiroki Kurata , Lu Zhou , Motonari Uesugi . Discovery of a self-assembling small molecule that sequesters RNA-binding proteins. Chinese Chemical Letters, 2025, 36(5): 110135-. doi: 10.1016/j.cclet.2024.110135
11. [11]
  Mengfan Zhang , Lingyan Liu , Peng Wei , Wei Feng , Tao Yi . A proximity tagging strategy utilizing an activated aldehyde group as the active site. Chinese Chemical Letters, 2025, 36(4): 110127-. doi: 10.1016/j.cclet.2024.110127
12. [12]
  Xueling Yu , Lixing Fu , Tong Wang , Zhixin Liu , Na Niu , Ligang Chen . Multivariate chemical analysis: From sensors to sensor arrays. Chinese Chemical Letters, 2024, 35(7): 109167-. doi: 10.1016/j.cclet.2023.109167
13. [13]
  Tiantian Long , Hongmei Luo , Jingbo Sun , Fengniu Lu , Yi Chen , Dong Xu , Zhiqin Yuan . Carbonization-engineered ultrafast chemical reaction on nanointerface. Chinese Chemical Letters, 2025, 36(3): 109728-. doi: 10.1016/j.cclet.2024.109728
14. [14]
  Yuqing Wang , Zhemin Li , Qingjun Lu , Qizhao Li , Jiaxin Luo , Chengjie Li , Yongshu Xie . Solar cells based on doubly concerted companion dyes with the efficiencies modulated by inserting an ethynyl group at different positions. Chinese Chemical Letters, 2024, 35(5): 109093-. doi: 10.1016/j.cclet.2023.109093
15. [15]
  Run-Han Li , Tian-Yi Dang , Wei Guan , Jiang Liu , Ya-Qian Lan , Zhong-Min Su . Evolution exploration and structure prediction of Keggin-type group IVB metal-oxo clusters. Chinese Chemical Letters, 2024, 35(5): 108805-. doi: 10.1016/j.cclet.2023.108805
16. [16]
  Junchen Peng , Xue Yin , Dandan Dong , Zhongyuan Guo , Qinqin Wang , Minmin Liu , Fei He , Bin Dai , Chaofeng Huang . Promotion effect of epoxy group neighboring single-atom Cu site on acetylene hydrochlorination. Chinese Chemical Letters, 2024, 35(6): 109508-. doi: 10.1016/j.cclet.2024.109508
17. [17]
  Yu-Yu Tan , Lin-Heng He , Wei-Min He . Copper-mediated assembly of SO₂F group via radical fluorine-atom transfer strategy. Chinese Chemical Letters, 2024, 35(9): 109986-. doi: 10.1016/j.cclet.2024.109986
18. [18]
  Wenyu Gao , Liming Zhang , Chuang Zhao , Lixiang Liu , Xingran Yang , Jinbo Zhao . Controlled semi-Pinacol rearrangement on a strained ring: Efficient access to multi-substituted cyclopropanes by group migration strategy. Chinese Chemical Letters, 2024, 35(9): 109447-. doi: 10.1016/j.cclet.2023.109447
19. [19]
  Chao LIU , Jiang WU , Zhaolei JIN . Synthesis, crystal structures, and antibacterial activities of two zinc(Ⅱ) complexes bearing 5-phenyl-1H-pyrazole group. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1986-1994. doi: 10.11862/CJIC.20240153
20. [20]
  Wei-Bin Li , Xiao-Chao Huang , Pei Liu , Jie Kong , Guo-Ping Yang . Recent advances in directing group assisted transition metal catalyzed para-selective C-H functionalization. Chinese Chemical Letters, 2025, 36(6): 110543-. doi: 10.1016/j.cclet.2024.110543

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(12)
HTML views(1)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142