2. Academic Validation
  3. Self-splicing RNA circularization facilitated by intact group I and II introns

Self-splicing RNA circularization facilitated by intact group I and II introns

  • Nat Commun. 2025 Aug 10;16(1):7376. doi: 10.1038/s41467-025-62607-y.
Yong Shen # 1 2,  Bohan Li # 1,  Lei Dong 3,  Wei Tang 1 2,  Jiwu Ren 1 2 3,  Feng Chen 1 2 3,  Wenjuan Zheng 1,  Ying Yu 1,  Lu Gao 4,  Wensheng Wei 5 6
Affiliations

Affiliations

  • 1 Biomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Peking University, Beijing, P.R. China.
  • 2 Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, P.R. China.
  • 3 Changping Laboratory, Beijing, P.R. China.
  • 4 Therorna Inc., Beijing, P.R. China.
  • 5 Biomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Peking University, Beijing, P.R. China. wswei@pku.edu.cn.
  • 6 Changping Laboratory, Beijing, P.R. China. wswei@pku.edu.cn.
  • # Contributed equally.
PMID: 40784880 DOI: 10.1038/s41467-025-62607-y
Abstract

Circular RNA (circRNA) has gained significant attention in RNA therapeutics due to its enhanced stability and protein-coding potential. In this study, we present two in vitro RNA circularization techniques, namely Permuted Intron-Exon through Trans-splicing (PIET) and Complete self-splicing Intron for RNA Circularization (CIRC). PIET leverages the second step of group I intron splicing, offering an alternative circularization strategy. CIRC utilizes the natural, intact forms of group I and group II introns, eliminating the need for intron engineering. Compared to Permuted Intron-Exon (PIE), CIRC exhibits enhanced RNA circularization efficiency and speed under mild conditions. Using CIRC, we successfully circularize large RNA constructs encoding full-length Dystrophin, a protein whose deficiency is linked to Duchenne muscular dystrophy (DMD), thus overcoming size limitations typically associated with circRNA platforms. Notably, CIRC enables the production of scarless circRNA and circRNA with minimal immunogenicity. Additionally, CIRC supports streamlined circRNA purification using ribonuclease R (RNase R) or oligo(dT)-based methods. These advancements significantly expand the potential of the circRNA platform for both research and therapeutic applications.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z