“Bind, cleave and leave”: multiple turnover catalysis of RNA cleavage by bulge–loop inducing supramolecular conjugates Article Swipe
Bahareh Amirloo
,
Yaroslav Staroseletz
,
Sameen Yousaf
,
David Clarke
,
Tom Brown
,
Harmesh Aojula
,
Marina A. Zenkova
,
Elena V. Bichenkova
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1093/nar/gkab1273
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1093/nar/gkab1273
Antisense sequence-specific knockdown of pathogenic RNA offers opportunities to find new solutions for therapeutic treatments. However, to gain a desired therapeutic effect, the multiple turnover catalysis is critical to inactivate many copies of emerging RNA sequences, which is difficult to achieve without sacrificing the sequence-specificity of cleavage. Here, engineering two or three catalytic peptides into the bulge–loop inducing molecular framework of antisense oligonucleotides achieved catalytic turnover of targeted RNA. Different supramolecular configurations revealed that cleavage of the RNA backbone upon sequence-specific hybridization with the catalyst accelerated with increase in the number of catalytic guanidinium groups, with almost complete demolition of target RNA in 24 h. Multiple sequence-specific cuts at different locations within and around the bulge–loop facilitated release of the catalyst for subsequent attacks of at least 10 further RNA substrate copies, such that delivery of only a few catalytic molecules could be sufficient to maintain knockdown of typical RNA copy numbers. We have developed fluorescent assay and kinetic simulation tools to characterise how the limited availability of different targets and catalysts had restrained catalytic reaction progress considerably, and to inform how to accelerate the catalytic destruction of shorter linear and larger RNAs even further.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/nar/gkab1273
- https://academic.oup.com/nar/article-pdf/50/2/651/42269817/gkab1273.pdf
- OA Status
- gold
- Cited By
- 7
- References
- 108
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4206943827
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4206943827Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/nar/gkab1273Digital Object Identifier
- Title
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“Bind, cleave and leave”: multiple turnover catalysis of RNA cleavage by bulge–loop inducing supramolecular conjugatesWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-12-14Full publication date if available
- Authors
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Bahareh Amirloo, Yaroslav Staroseletz, Sameen Yousaf, David Clarke, Tom Brown, Harmesh Aojula, Marina A. Zenkova, Elena V. BichenkovaList of authors in order
- Landing page
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https://doi.org/10.1093/nar/gkab1273Publisher landing page
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https://academic.oup.com/nar/article-pdf/50/2/651/42269817/gkab1273.pdfDirect link to full text PDF
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YesWhether a free full text is available
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-
goldOpen access status per OpenAlex
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https://academic.oup.com/nar/article-pdf/50/2/651/42269817/gkab1273.pdfDirect OA link when available
- Concepts
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RNA, Biology, Oligonucleotide, Cleavage (geology), Cleave, Gene knockdown, Catalysis, Ribozyme, Combinatorial chemistry, Molecular biology, Computational biology, Biochemistry, Gene, DNA, Chemistry, Fracture (geology), PaleontologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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7Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2, 2024: 3, 2022: 2Per-year citation counts (last 5 years)
- References (count)
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108Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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