Nature's recipe for splitting inteins
Open accessAbstract
Protein splicing in trans by split inteins has increasingly become a powerful protein-engineering tool for protein ligation, both in vivo and in vitro. Over 100 naturally occurring and artificially engineered split inteins have been reported for protein ligation using protein trans-splicing. Here, we review the current status of the reported split inteins in order to delineate an empirical or rational strategy for constructing new split inteins suitable for various applications in biotechnology and chemical biology.
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Protein trans-splicing joins two separate polypeptides into one through a peptide bond, mediated by inteins.
“In fact, protein trans-splicing consists of joining two separate polypeptides into one through a peptide bond [56].”
From Circumventing the packaging limit of AAV-mediated gene replacement therapy for neurological disorders (2022) · cites this paper as [56]
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Inteins: nature's gift to protein chemists
Shah, N. H., & Muir, T. W. (2014) · Chem. Sci. · doi:10.1039/c3sc52951g · Cited by 404 · see citing works
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Adeno-associated virus vector as a platform for gene therapy delivery
Wang, D., Tai, P. W. L., & Gao, G. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0012-9 · Cited by 2,444 · see citing works
Dual-AAV delivering split prime editor system for in vivo genome editing
Zhi, S., Chen, Y., Wu, G., Wen, J., Wu, J., Liu, Q., Li, Y., Kang, R., Hu, S., Wang, J., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2021.07.011 · Cited by 174 · see citing works
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“artificial split inteins are available to date [65], and their size ranges between 129 and >1000 residues [56].”
BackgroundSplit AAV8 Mediated ABCA4 Expression for Gene Therapy of Mouse Stargardt Disease (STGD1)
Li, R., Jing, Q., She, K., Wang, Q., Jin, X., Zhao, Q., Su, J., Song, L., Fu, J., Wu, X., et al. (2023) · Human Gene Therapy · doi:10.1089/hum.2023.017 · Cited by 21 · see citing works
Evolution of prime editing systems: move forward to the treatment of hereditary diseases
Volodina, O. V., Fabrichnikova, A. R., Anuchina, A. A., Mishina, O. S., Lavrov, A. V., & Smirnikhina, S. A. (2025) · Current Gene Therapy · doi:10.2174/0115665232295117240405070809 · Cited by 1 · see citing works
- Authors
- Aranko, A. S., Wlodawer, A., & Iwai, H.
- Affiliations
- University of Helsinki (FI)
- National Cancer Institute (US)
- Venue
- Protein Engineering Design and Selection
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-08-01
- Volume
- 27
- Issue
- 8
- Pages
- 263-271
- ISSN
- 0269-2139 (ISSN-L)
- 1741-0126
- 1741-0134
- PMC
- PMC4133565
- OpenAlex
- W2056881013
- Cited by
- 116
- References
- 1
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 12 · 2023: 15 · 2022: 11 · 2021: 16 · 2020: 21 · 2019: 9 · 2018: 8 · 2017: 4 · 2016: 9 · 2015: 3
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Protein Engineering Design and Selection (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Academy of Finland (137995)
- Biocenter Finland
- National Institutes of Health
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- split intein, protein trans-splicing, protein ligation, protein engineering, chemical biology
- MeSH terms
- Animals, Humans, Models, Molecular, Protein Splicing, Trans-Splicing, Inteins
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