DNA Framework–Programmed Nanoscale Enzyme Assemblies DOI

Nan Cao,

Ruiyan Guo, Ping Song

et al.

Nano Letters, Journal Year: 2024, Volume and Issue: 24(15), P. 4682 - 4690

Published: April 2, 2024

Multienzyme assemblies mediated by multivalent interaction play a crucial role in cellular processes. However, the three-dimensional (3D) programming of an enzyme complex with defined activity vitro remains unexplored, primarily owing to limitations precisely controlling spatial topological configuration. Herein, we introduce nanoscale 3D assembly using tetrahedral DNA framework (TDF), enabling replication configuration and maintenance identical edge-to-edge distance akin natural enzymes. Our results demonstrate that both two-enzyme systems (glucose oxidase (GOx)/horseradish peroxidase (HRP)) three-enzyme (amylglucosidase (AGO)/GOx/HRP) lead enhanced cascade catalytic compared low-dimensional structure, resulting ∼5.9- ∼7.7-fold enhancements over homogeneous diffusional mixtures free enzymes, respectively. Furthermore, for detection metabolism biomarkers creatinine creatine, achieving low limit detection, high sensitivity, broad range.

Language: Английский

DNA as a universal chemical substrate for computing and data storage DOI
Shuo Yang, Bas W. A. Bögels, Fei Wang

et al.

Nature Reviews Chemistry, Journal Year: 2024, Volume and Issue: 8(3), P. 179 - 194

Published: Feb. 9, 2024

Language: Английский

Citations

40
A Programmable DNAzyme for the Sensitive Detection of Nucleic Acids DOI

Chenzhi Shi,

Donglei Yang, Xiaowei Ma

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(12)

Published: Jan. 30, 2024

Nucleic acids in biofluids are emerging biomarkers for the molecular diagnostics of diseases, but their clinical use has been hindered by lack sensitive detection assays. Herein, we report development a nucleic acid assay named SPOT (sensitive loop-initiated DNAzyme biosensor detection) rationally designing catalytic endonuclease capability into unified one-stranded allosteric biosensor. is activated once target specific sequence binds to its module enable continuous cleavage reporters. provides highly robust platform sensitive, convenient and cost-effective low-abundance acids. For validation, demonstrated that could detect serum miRNAs breast cancer, gastric cancer prostate cancer. Furthermore, exhibits potent performance over SARS-CoV-2 RNA from swabs with high sensitivity specificity. Finally, compatible point-of-care testing modalities such as lateral flow Hence, envision may serve variety targets enabling clinics.

Language: Английский

Citations

33
Leveraging Aptamer-Based DNA Nanotechnology for Bioanalysis and Cancer Therapeutics DOI Creative Commons
Zhiyong Huang, Dan Wang, Qiang Zhang

et al.

Accounts of Materials Research, Journal Year: 2024, Volume and Issue: 5(4), P. 438 - 452

Published: March 14, 2024

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

Language: Английский

Citations

33
Buoyant Metal–Organic Framework Corona-Driven Fast Isolation and Ultrasensitive Profiling of Circulating Extracellular Vesicles DOI

Xiaojie Qin,

Yuanhang Xiang, Linfeng Mao

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(22), P. 14569 - 14582

Published: May 23, 2024

Accurately assaying tumor-derived circulating extracellular vesicles (EVs) is fundamental in noninvasive cancer diagnosis and therapeutic monitoring but limited by challenges efficient EV isolation profiling. Here, we report a bioinspired buoyancy-driven metal-organic framework (MOF) corona that leverages on-bubble coordination dual-encoded surface-enhanced Raman scattering (SERS) nanotags to streamline rapid ultrasensitive profiling of plasma EVs single assay for diagnostics. This integrated bubble-MOF-SERS (IBMsv) allows barnacle-like high-density adhesion MOFs on self-floating bubble surface enable fast (2 min, near 90% capture efficiency) tumor via enhanced EV-MOF binding. Also, IBMsv harnesses four-plexed SERS profile the captured protein markers at single-particle level. Such sensitive multiplexed across five types, revealing heterogeneous expression patterns. Furthermore, enables pilot clinical cohort (

Language: Английский

Citations

22
A spatially localized DNA linear classifier for cancer diagnosis DOI Creative Commons

Linlin Yang,

Qian Tang, Mingzhi Zhang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 29, 2024

Abstract Molecular computing is an emerging paradigm that plays essential role in data storage, bio-computation, and clinical diagnosis with the future trends of more efficient scheme, higher modularity scaled-up circuity stronger tolerance corrupted inputs a complex environment. Towards these goals, we construct spatially localized, DNA integrated circuits-based classifier (DNA IC-CLA) can perform neuromorphic architecture-based computation at molecular level for medical diagnosis. The DNA-based employs two-dimensional origami as framework localized processing modules in-frame core to execute arithmetic operations (e.g. multiplication, addition, subtraction) linear classification patterns miRNA inputs. We demonstrate IC-CLA enables accurate cancer faster (about 3 h) effective manner synthetic samples compared those traditional freely diffusible circuits. believe this all-in-one exhibit applications biocomputing cells diagnostics.

Language: Английский

Citations

21
Agarose Gel‐Coated Nanochannel Biosensor for Detection of Prostate‐Specific Antigen in Unprocessed Whole Blood Samples DOI
Jing Zhao, Yuling Xiao, Mengyu Yang

et al.

Small, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract Solid‐state nanopore/nanochannel biosensors have rapidly advanced due to their high sensitivity, label‐free detection, and fast response. However, detecting biomarkers directly in complex biological environments, particularly whole blood, remains challenging because of nonspecific protein adsorption clogging. Here, a DNA aptamer functionalized nanochannel biosensor is developed with excellent antifouling properties, achieved by coating the surface agarose gel. This gel effectively mitigates fouling diverse environments while maintaining comparable sensitivity uncoated nanochannels for prostate‐specific antigen (PSA) buffer solutions within 20 min. The exhibits detection limit 1 ng mL −1 PSA human serum, matching performance commercial enzyme‐linked immunosorbent assay (ELISA) kits. Importantly, it successfully differentiates blood samples from prostate cancer patients healthy individuals. superior behavior attributed electrically neutral, highly hydrophilic nature, porous structure gel, which prevents large biomolecules facilitating diffusion aptamer‐based capture. offers reliable showing great promise biomedical applications.

Language: Английский

Citations

2
Spatially Localized Entropy-Driven Evolution of Nucleic Acid-Based Constitutional Dynamic Networks for Intracellular Imaging and Spatiotemporal Programmable Gene Therapy DOI Creative Commons
Nina Lin, Yu Ouyang,

Yunlong Qin

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(30), P. 20685 - 20699

Published: July 16, 2024

The primer-guided entropy-driven high-throughput evolution of the DNA-based constitutional dynamic network, CDN, is introduced. entropy gain associated with process provides a catalytic principle for amplified emergence CDN. concept applied to develop programmable, spatially localized DNA circuit effective in vitro and vivo theranostic, gene-regulated treatment cancer cells. consists tetrahedron core modified at its corners four tethers that include encoded base sequences exhibiting capacity emerge assemble into [2 × 2] Two are caged by pair siRNA subunits, blocking mute, dynamically inactive configuration. In presence miRNA-21 as primer, subunits displaced, resulting release siRNAs silencing HIF-1α mRNA fast reconfiguration CDN is, however, engineered be reconfigured miRNA-155 an equilibrated mixture enriched DNAzyme component, catalyzing cleavage EGR-1 mRNA. nanostructure stimulates enhanced permeation miRNA-triggered leads cooperative bis-gene-silencing mRNAs, selective apoptosis breast cells inhibition tumors tumor bearing mice.

Language: Английский

Citations

16
Machine Learning-Assistant Colorimetric Sensor Arrays for Intelligent and Rapid Diagnosis of Urinary Tract Infection DOI
Jianyu Yang, Ge Li, Shihong Chen

et al.

ACS Sensors, Journal Year: 2024, Volume and Issue: 9(4), P. 1945 - 1956

Published: March 26, 2024

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 emergence of drug-resistant pathogens. Current diagnostic strategies for UTIs, such as urine culture flow cytometry, require time-consuming protocols expensive equipment. We present here machine learning-assisted colorimetric sensor array based on recognition ligand-functionalized Fe single-atom nanozymes (SANs) identification microorganisms at order, genus, species levels. Colorimetric arrays built from SAN Fe1–NC functionalized four types ligands, generating unique microbial fingerprints. By integrating trained computational classification model, platform identify more than 10 UTI samples within 1 h. Diagnostic accuracy up 97% was achieved 60 clinical samples, holding great potential translation into practice applications.

Language: Английский

Citations

15
Functionalized tetrahedral DNA frameworks for the capture of circulating tumor cells DOI
Yi‐Rong Chen, Meihua Lin, Dekai Ye

et al.

Nature Protocols, Journal Year: 2024, Volume and Issue: 19(4), P. 985 - 1014

Published: Feb. 5, 2024

Language: Английский

Citations

14
Advances in Machine Learning Processing of Big Data from Disease Diagnosis Sensors DOI
Shasha Lu, Jianyu Yang, Yu Gu

et al.

ACS Sensors, Journal Year: 2024, Volume and Issue: 9(3), P. 1134 - 1148

Published: Feb. 16, 2024

Exploring accurate, noninvasive, and inexpensive disease diagnostic sensors is a critical task in the fields of chemistry, biology, medicine. The complexity biological systems explosive growth biomarker data have driven machine learning to become powerful tool for mining processing big from diagnosis sensors. With development bioinformatics artificial intelligence (AI), models formed by been able guide more sensitive accurate molecular computing. This review presents an overview collection approaches fundamental algorithms discusses recent advances computational More specifically, we highlight existing modular workflows key opportunities challenges achieve through mining.

Language: Английский

Citations

13