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
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