An automated DNA computing platform for rapid etiological diagnostics

Ma, Qian; Zhang, Mingzhi; Zhang, Chao; Teng, Xiaoyan; Yang, Linlin; Tian, Yuan; Wang, Junyan; Han, Da; Tan, Weihong

doi:10.1126/sciadv.ade0453

Cited by 22 publications

(14 citation statements)

References 46 publications

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“…Three types of molecular computation formulation were discussed in this section. The first molecular computing formulation is based on weight operation . For example, based on an in silico computationally trained classifier and DNA computation, Han and the colleagues achieved rapid and accurate lung cancer diagnosis with microRNA inputting using clinical serum samples .…”

Section: Aptamer-based Bioanalysismentioning

confidence: 99%

Leveraging Aptamer-Based DNA Nanotechnology for Bioanalysis and Cancer Therapeutics

Huang,

Wang,

Zhang

et al. 2024

Acc. Mater. Res.

Self Cite

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Metrics & More Article Recommendations CONSPECTUS: Aptamers are single-stranded DNA or RNA molecules composed of 15−80 nucleotides, obtained from a random oligonucleotide library via the systematic evolution of ligands by exponential enrichment (SELEX) technology. They can bind to a wide range of targets with high binding affinity and high specificity including metal ions, small molecules, proteins, cells, and even tissues. When compared to the commonly used antibodies, aptamers show better thermal stability, a smaller molecular weight, easier modification, and little batch-to-batch variation by chemical synthesis. These unique merits position aptamers as promising molecular tools in biomedical applications, spanning biosensing, bioimaging, disease diagnosis, targeted chemotherapy, and cancer immunotherapy. However, as chemically synthesized oligonucleotides, aptamers would be degraded by nucleic acid degrading enzymes (e.g., endonucleases or exonucleases) presented in the blood circulation, thereby reducing the stability and activity. Another limitation is the rapid clearance by the liver and kidneys, reducing their circulation life and bioavailability. Recent progress in DNA nanotechnology has garnered global interest, with emerging interdisciplinary applications across chemistry, materials, biology, and medicine. The fundamental of DNA selfassemblies and DNA dynamic operation is Watson−Crick base pairing assisted by in silico programmable design. As functional building blocks, aptamers can inherently enable great potential with DNA nanotechnology including bioanalysis, targeted drug delivery, and cancer immunotherapy. Therefore, aptamer-based DNA nanotechnology would arouse important interests in future research. As molecular medicine offered personalized and precise diagnostic and therapeutic solutions, in this Account, we focus on the research advancements of leveraging DNA aptamer with DNA nanotechnology for molecular medicine, particularly our recent research progress. Often referred to as chemical antibodies, aptamers enable DNA nanotechnology for bioanalysis and cancer therapeutics. Thus, two parts are discussed in this Account: initially, we discuss the molecular modifications of aptamers by cyclization and nucleotide backbone engineering. The aptamer-tethered DNA nanostructures then were constructed for cell identification and bioanalysis. To perform intelligent cancer diagnosis, we detailed three formulations of aptamer-involved molecular computation. In the last part, we focus on aptamer-based targeted chemotherapy and immunotherapy. Based on the covalent coupling strategy, we report a series of aptamer drug conjugates. Similarly, by employing cyclization strategy, the circular bivalent aptamer drug conjugates are discussed. Next, as small molecule drug delivery systems encounter challenges related to insufficient biological stability, particularly in terms of vulnerability to enzyme cleavage and short circulation time in vivo, aptamer-tethered nanomedicines are introduced for targeted chemotherapy. ...

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Section: Aptamer-based Bioanalysismentioning

confidence: 99%

Leveraging Aptamer-Based DNA Nanotechnology for Bioanalysis and Cancer Therapeutics

Huang,

Wang,

Zhang

et al. 2024

Acc. Mater. Res.

Self Cite

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“…(c) Scheme of an intelligent DNA-based genetic decoder. [51] Graph copyright from reference [49][50][51] .…”

Section: Challenges and Opportunitiesmentioning

confidence: 99%

“…On the bias of the approach, they also developed an automated DNA computing‐based platform for acute respiratory infections (ARI) etiology diagnostics and obtained a diagnostic accuracy of 87% in 80 clinical samples without demanding technicians (Figure 7b). [50] Permutation of single‐nucleotide polymorphisms is a kind of variation of nucleic acids, which can lead to a series of phenotypic consequences including human diseases or pathogenic drug resistance. Therefore, they built a programmable DNA decoding circuit to facilitate the translation of complex genetic profiles into actionable medical decisions (Figure 7c).…”

Section: Cell Biomarker For Differentiating Subtypes Of Cancer Based ...mentioning

confidence: 99%

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Smart DNA sensors‐based molecular identification for cancer subtyping

Gao,

Xiong,

Gong

et al. 2023

Smart Molecules

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Molecular subtyping of cancer can greatly help to understand the development of disease and predict tumor behavior. Exploring detection methods for precise subtyping is appealing to prognosis and personalized therapy. During the past decades, DNA‐based biosensors have exhibited great potential in cancer diagnosis due to their structural programmability and functional diversity. Despite the encouraging progress that has been made, there remains an issue in improving the accuracy and sensitivity of cancer subtyping due to the complex process of disease, especially in preclinical or clinical applications. To accelerate the development of DNA sensors in the identification of cancer subtypes, in this review, we summarized their advances in molecular subtyping by analyzing the heterogeneity in categories and levels of biomarkers between cancer subtypes. The strategies toward genomic and proteomic heterogeneity in cells or on the cell surface, as well as the cancer excretions including extracellular vesicles (EVs) and microRNA (miRNAs) in serum, are summarized. Current challenges and the opportunities of DNA‐based sensors in this field are also discussed.

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“…36,37 More recently, support vector machine, random forest, and other supervised learning methods have been applied to construct the detection model for microbial analysis and disease diagnosis. 38,39 Thus, the synergistic combination of machine learning algorithms and optical sensing arrays with SANs allows the building of an intelligent nanoplatform for rapid and reliable identification of UTI types.…”

mentioning

confidence: 99%

Machine Learning-Assistant Colorimetric Sensor Arrays for Intelligent and Rapid Diagnosis of Urinary Tract Infection

Yang,

Li,

Chen

et al. 2024

ACS Sens.

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Urinary tract infections (UTIs), which can lead to pyelonephritis, urosepsis, and even death, are among the most prevalent infectious diseases worldwide, with a notable increase in treatment costs due to the emergence of drug-resistant pathogens. Current diagnostic strategies for UTIs, such as urine culture and flow cytometry, require timeconsuming protocols and expensive equipment. We present here a machine learning-assisted colorimetric sensor array based on recognition of ligand-functionalized Fe single-atom nanozymes (SANs) for the identification of microorganisms at the order, genus, and species levels. Colorimetric sensor arrays are built from the SAN Fe 1 −NC functionalized with four types of recognition ligands, generating unique microbial identification fingerprints. By integrating the colorimetric sensor arrays with a trained computational classification model, the platform can identify more than 10 microorganisms in UTI urine samples within 1 h. Diagnostic accuracy of up to 97% was achieved in 60 UTI clinical samples, holding great potential for translation into clinical practice applications.

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An automated DNA computing platform for rapid etiological diagnostics

Cited by 22 publications

References 46 publications

Leveraging Aptamer-Based DNA Nanotechnology for Bioanalysis and Cancer Therapeutics

Leveraging Aptamer-Based DNA Nanotechnology for Bioanalysis and Cancer Therapeutics

Smart DNA sensors‐based molecular identification for cancer subtyping

Machine Learning-Assistant Colorimetric Sensor Arrays for Intelligent and Rapid Diagnosis of Urinary Tract Infection

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