The double life of CRISPR–Cas13
Open accessAbstract
Since the discovery of RNA-programmable nucleases from the prokaryotic adaptive immune system CRISPR-Cas, these proteins have seen rapid and widespread adoption for biotechnological and clinical research. A recently discovered system, CRISPR-Cas13, uses CRISPR RNA guides to target RNA. Interestingly, RNA targeting by Cas13 results in cleavage of both target RNA and bystander RNA. This feature has been used to develop innovative diagnostic tools for the detection of specific RNAs. Unlike in vitro detection of RNA using collateral RNA cleavage, however, initial studies of mammalian cells only revealed highly specific target RNA-knockdown activity. Although these findings have been confirmed subsequently, several recent publications do report Cas13-mediated toxicity and collateral RNA cleavage when using Cas13 in eukaryotes. Here, we review these conflicting observations and discuss its potential molecular basis.
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The exact specificity profile of CasRx remains contested.
“and the exact specificity profile of CasRx remains contested (10).”
From Characterization of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina (2024) · cites this paper as [10]
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Characterization of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina
Kumar, S., Hsiao, Y.-W., Wong, V. H. Y., Aubin, D., Wang, J.-H., Lisowski, L., Rakoczy, E. P., Li, F., Alarcon-Martinez, L., Gonzalez-Cordero, A., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2408345121 · Cited by 19 · see citing works
- Authors
- Bot, J. F., van der Oost, J., & Geijsen, N.
- Affiliations
- Leiden University Medical Center (NL)
- Corresponding author
- Geijsen, Niels
- Venue
- Current Opinion in Biotechnology
- Publisher
- Elsevier BV
- Published
- 2022-12
- Volume
- 78
- Pages
- 102789
- ISSN
- 0958-1669 (ISSN-L)
- OpenAlex
- W4295788291
- Cited by
- 50
- References
- 3
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 21 · 2023: 5
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Opinion in Biotechnology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Funders
- Novo Nordisk (NNF21CC0073729)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- CRISPR-Cas13, RNA knockdown, prokaryotic adaptive immunity
- MeSH terms
- Gene Editing, Animals, Mammals, RNA, CRISPR-Cas Systems
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