ArticleProceedings of the National Academy of Sciences of the United States of America2015
Detecting cancers through tumor-activatable minicircles that lead to a detectable blood biomarker.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- Dual-biomarkers encoding tumor-activatable minicircles with scaffold/matrix attachment region motif for sensitive and sustained blood and urine-based cancer detection.Cancer cell international · 2026Article
- Artificially Engineered Synthetic Biomarkers Revolutionizing Early Diagnosis of Diseases.Molecules (Basel, Switzerland) · 2025Review
- Evaluation of DNA minicircles for delivery of adenine and cytosine base editors using activatable gene on "GO" reporter imaging systems.Molecular therapy. Nucleic acids · 2024Article
- Targeting and monitoring ovarian cancer invasion with an RNAi and peptide delivery system.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Inhalable point-of-care urinary diagnostic platform.Science advances · 2024Article
- Programmable eukaryotic protein synthesis with RNA sensors by harnessing ADAR.Nature biotechnology · 2023Article
- Review
- The Need to Pair Molecular Monitoring Devices with Molecular Imaging to Personalize Health.Molecular imaging and biology · 2022Review
- Cancer Detection Using an Artificial Secretable MicroRNA Found in Blood and Urine.Biomedicines · 2022Article
- Microenvironment-triggered multimodal precision diagnostics.Nature materials · 2021Article
- Synthetic biomarkers: a twenty-first century path to early cancer detection.Nature reviews. Cancer · 2021Review
- Synthetic Circuit-Driven Expression of Heterologous Enzymes for Disease Detection.ACS synthetic biology · 2021Article
- Minicircles for a two-step blood biomarker and PET imaging early cancer detection strategy.Journal of controlled release : official journal of the Controlled Release Society · 2021Article
- A survivin-driven, tumor-activatable minicircle system for prostate cancer theranostics.Molecular therapy oncolytics · 2021Article
- Base-pair resolution analysis of the effect of supercoiling on DNA flexibility and major groove recognition by triplex-forming oligonucleotides.Nature communications · 2021Article
- Activity-Based Diagnostics: An Emerging Paradigm for Disease Detection and Monitoring.Trends in molecular medicine · 2020Review
- Macrophage Sensors for Early Cancer Detection.Clinical chemistry · 2020Article
- Microvesicle-Mediated Delivery of Minicircle DNA Results in Effective Gene-Directed Enzyme Prodrug Cancer Therapy.Molecular cancer therapeutics · 2019Article
- Long non-coding RNA NEF inhibits proliferation and promotes apoptosis of laryngeal squamous cell carcinoma cells by inhibiting Wnt/β-catenin signaling.Oncology letters · 2019Article
- Engineered immune cells as highly sensitive cancer diagnostics.Nature biotechnology · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Earlier detection of cancers can dramatically improve the efficacy of available treatment strategies. However, despite decades of effort on blood-based biomarker cancer detection, many promising endogenous biomarkers have failed clinically because of intractable problems such as highly variable background expression from nonmalignant tissues and tumor heterogeneity. In this work we present a tumor-detection strategy based on systemic administration of tumor-activatable minicircles that use the pan-tumor-specific Survivin promoter to drive expression of a secretable reporter that is detectable in the blood nearly exclusively in tumor-bearing subjects. After systemic administration we demonstrate a robust ability to differentiate mice bearing human melanoma metastases from tumor-free subjects for up to 2 wk simply by measuring blood reporter levels. Cumulative change in reporter levels also identified tumor-bearing subjects, and a receiver operator-characteristic curve analysis highlighted this test's performance with an area of 0.918 ± 0.084. Lung tumor burden additionally correlated (r(2) = 0.714; P < 0.05) with cumulative reporter levels, indicating that determination of disease extent was possible. Continued development of our system could improve tumor detectability dramatically because of the temporally controlled, high reporter expression in tumors and nearly zero background from healthy tissues. Our strategy's highly modular nature also allows it to be iteratively optimized over time to improve the test's sensitivity and specificity. We envision this system could be used first in patients at high risk for tumor recurrence, followed by screening high-risk populations before tumor diagnosis, and, if proven safe and effective, eventually may have potential as a powerful cancer-screening tool for the general population.
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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.