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DNAzyme-based faithful probing and pulldown to identify candidate biomarkers of low abundance.
- Source :
-
Nature chemistry [Nat Chem] 2024 Jan; Vol. 16 (1), pp. 122-131. Date of Electronic Publication: 2023 Sep 14. - Publication Year :
- 2024
-
Abstract
- Biomarker discovery is essential for the understanding, diagnosis, targeted therapy and prognosis assessment of malignant diseases. However, it remains a huge challenge due to the lack of sensitive methods to identify disease-specific rare molecules. Here we present MORAC, molecular recognition based on affinity and catalysis, which enables the effective identification of candidate biomarkers with low abundance. MORAC relies on a class of DNAzymes, each cleaving a sole RNA linkage embedded in their DNA chain upon specifically sensing a complex system with no prior knowledge of the system's molecular content. We show that signal amplification from catalysis ensures the DNAzymes high sensitivity (for target probing); meanwhile, a simple RNA-to-DNA mutation can shut down their RNA cleavage ability and turn them into a pure affinity tool (for target pulldown). Using MORAC, we identify previously unknown, low-abundance candidate biomarkers with clear clinical value, including apolipoprotein L6 in breast cancer and seryl-tRNA synthetase 1 in polyps preceding colon cancer.<br /> (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
- Subjects :
- DNA
RNA
Biomarkers
DNA, Catalytic genetics
Biosensing Techniques
Subjects
Details
- Language :
- English
- ISSN :
- 1755-4349
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 37710046
- Full Text :
- https://doi.org/10.1038/s41557-023-01328-5