ArticleNucleic acids research2020
Highly specific enrichment of rare nucleic acid fractions using Thermus thermophilus argonaute with applications in cancer diagnostics.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 141 citations in OpenAlex.
- Distinct Cleavage Trajectories Mediated by DNA and RNA Substrate in Argonaute From Methanocaldococcus Fervens.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A DNA-guided prokaryotic argonaute enables programmable RNA cleavage for sequencing and quality control ofMolecular therapy. Nucleic acids · 2026Article
- High-throughput evaluation of in vitro CRISPR activities enables optimized large-scale multiplex enrichment of rare variants.Nature biomedical engineering · 2026Article
- Moderate-temperature DNA cleavage activity of TtAgo activated by dCTP/TthSSB for one-step isothermal microRNAs detection.Nature communications · 2026Article
- PANDA: AND logic-gated RNA sensing enabled by a photo-activated RCA-Argonaute cascade.Chemical science · 2026Article
- Single-nucleotide variant profiling in liquid biopsy with RECO-Cas.Science advances · 2026Article
- SIM: Discovery of novel RNA-targeting argonautes by self-iterative learning from scarce data.Acta pharmaceutica Sinica. B · 2026Article
- Article
- Ultrasensitive Detection of Rare Mutations via Amplifying-Cleaving-Enriching in Acute Myeloid Leukemia.Biomedicines · 2025Article
- Programmable Argonaute-mediated single-nucleotide variant sequencing of cell-free DNA for multi-cancer early detection.Nature communications · 2025Article
- Programmable fluorescent aptamer-based RNA switches for rapid identification of point mutations.Nature chemistry · 2025Article
- A programmable pAgo nuclease with high activity and specificity for efficient DNA and RNA manipulation.Communications biology · 2025Article
- Comment on: "Atom-Modified gDNA Enhances Cleavage Activity of TtAgo Enabling Ultrasensitive Nucleic Acid Testing".Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NAPTUNE: nucleic acids and protein biomarkers testing via ultra-sensitive nucleases escalation.Nature communications · 2025Article
- Multiplexed food-borne pathogen detection using an argonaute-mediated digital sensor based on a magnetic-bead-assisted imaging transcoding system.Nature food · 2025Article
- Advances in nucleic acid probe-based detection of gene point mutations: a review.Frontiers in chemistry · 2025Review
- A conditional protein diffusion model generates artificial programmable endonuclease sequences with enhanced activity.Cell discovery · 2024Article
- Pyrimidine-Dependent UV-Mediated Cross-Linking Magnifies Minor Genetic or Epigenetic Changes in Clinical Samples.Clinical chemistry · 2024Article
- PfAgo-based dual signal amplification biosensor for rapid and highly sensitive detection of alkaline phosphatase activity.Mikrochimica acta · 2024Article
- Atom-Modified gDNA Enhances Cleavage Activity of TtAgo Enabling Ultra-Sensitive Nucleic Acid Testing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Detection of disease-associated, cell-free nucleic acids in body fluids enables early diagnostics, genotyping and personalized therapy, but is challenged by the low concentrations of clinically significant nucleic acids and their sequence homology with abundant wild-type nucleic acids. We describe a novel approach, dubbed NAVIGATER, for increasing the fractions of Nucleic Acids of clinical interest Via DNA-Guided Argonaute from Thermus thermophilus (TtAgo). TtAgo cleaves specifically guide-complementary DNA and RNA with single nucleotide precision, greatly increasing the fractions of rare alleles and, enhancing the sensitivity of downstream detection methods such as ddPCR, sequencing, and clamped enzymatic amplification. We demonstrated 60-fold enrichment of the cancer biomarker KRAS G12D and ∼100-fold increased sensitivity of Peptide Nucleic Acid (PNA) and Xenonucleic Acid (XNA) clamp PCR, enabling detection of low-frequency (<0.01%) mutant alleles (∼1 copy) in blood samples of pancreatic cancer patients. NAVIGATER surpasses Cas9-based assays (e.g. DASH, Depletion of Abundant Sequences by Hybridization), identifying more mutation-positive samples when combined with XNA-PCR. Moreover, TtAgo does not require targets to contain any specific protospacer-adjacent motifs (PAM); is a multi-turnover enzyme; cleaves ssDNA, dsDNA and RNA targets in a single assay; and operates at elevated temperatures, providing high selectivity and compatibility with polymerases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.