Photochemically Triggered, Transient, and Oscillatory Transcription Machineries Guide Temporal Modulation of Fibrinogenesis DOI Creative Commons

Jiantong Dong,

Itamar Willner

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 31, 2024

Photochemically triggered, transient, and temporally oscillatory-modulated transcription machineries are introduced. The resulting dynamic circuits implemented to guide photochemically oscillatory modulation of thrombin toward temporal control over fibrinogenesis. One system describes the assembly a reaction module leading triggered formation an active machinery that, in presence RNase H, guides transient activation A second introduces photochemical triggering circuit consisting two coupled machineries, depletion intermediate product. concept is applied develop leads generation anti-thrombin aptamer-modified oscillating product induces rhythmic inhibition thrombin, accompanied by cyclic deactivation fibrinogenesis process. operation computational kinetic models, allowing predict behaviors under different auxiliary conditions. phototriggered circuit-guided examined physiological-like conditions within human plasma environment.

Language: Английский

All-In-One Entropy-Driven DNA Nanomachine for Tumor Cell-Selective Fluorescence/SERS Dual-Mode Imaging of MicroRNA DOI
Shuzhen Yue, Xuan Xu, Liping Jiang

et al.

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

An entropy-driven catalysis (EDC) strategy is appealing for amplified bioimaging of microRNAs in living cells; yet, complex operation procedures, lacking cell selectivity, and insufficient accuracy hamper its further applications. Here, we introduce an ingenious all-in-one DNA nanomachine (termed as AIO-EDN), which can be triggered by endogenous apurinic/apyrimidinic endonuclease 1 (APE1) to achieve tumor cell-selective dual-mode imaging microRNA. Compared with the traditional EDC strategy, integrated design AIO-EDN achieves autocatalytic signal amplification without extra fuel strands. Moreover, leverages APE1 overexpressed cancer cells activate reaction, which, however, exerts no target sensing activity normal cells. Combining fluorescence- surface-enhanced Raman scattering (FL/SERS) techniques, this exhibits significantly improved selectivity microRNA This study provides a new paradigm develop EDC-based platform shows great potential in-depth diagnosis high precision.

Language: Английский

Citations

1

Space-coded microchip for multiplexed respiratory virus detection via CRISPR-Cas12a and RPA DOI

Mengqiu Xiong,

Yao Wang,

Shuhan Lu

et al.

Talanta, Journal Year: 2025, Volume and Issue: 291, P. 127815 - 127815

Published: Feb. 27, 2025

Language: Английский

Citations

1

Photoactivatable CRISPR/Cas9 lateral flow strip platform for one-pot rapid detection of squamous cell carcinoma antigen DNA in blood DOI

Zeping Yang,

Bin Guo,

Chong Hu

et al.

Sensors and Actuators B Chemical, Journal Year: 2025, Volume and Issue: unknown, P. 137607 - 137607

Published: March 1, 2025

Language: Английский

Citations

1

Leveraging Synthetic Antibody–DNA Conjugates to Expand the CRISPR-Cas12a Biosensing Toolbox DOI
Elisa Paialunga,

N. Bagheri,

Marianna Rossetti

et al.

ACS Synthetic Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

We report here the use of antibody-DNA conjugates (Ab-DNA) to activate collateral cleavage activity CRISPR-Cas12a enzyme. Our findings demonstrate that Ab-DNA effectively trigger CRISPR-Cas12a, enabling transduction antibody-mediated recognition events into fluorescence outputs. developed two different immunoassays using an as activator Cas12a: CRISPR-based immunosensing assay (CIA) for detecting SARS-CoV-2 spike S protein, which shows superior sensitivity compared with traditional enzyme-linked immunosorbent (ELISA), and immunomagnetic (CIMA). Notably, CIMA successfully detected protein in undiluted saliva a limit detection (LOD) 890 pM 2 h assay. results underscore benefits integrating Cas12a-based signal amplification antibody methods. The potential conjugates, combined CRISPR technology, offers promising alternative conventional enzymes used could facilitate development versatile analytical platforms non-nucleic acid targets.

Language: Английский

Citations

0

Endogenous HClO-Gated Cascade MicroRNA Imaging for Precise Diagnosis of Atherosclerosis In Vivo DOI

Moxuan Ji,

Jiantong Dong,

Zhuo Ye

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Precise imaging of atherosclerotic plaques using biomarkers could prompt the diagnosis and clinical management atherosclerosis (AS)-driven cardiovascular diseases. MicroRNA-155 (miR-155) plays a critical role in AS development, with its expression notably upregulated foam cells within plaques. However, miRNA methods for face significant challenges, including low specificity, inefficient delivery, poor cell selectivity. Herein, we develop an endogenous hypochlorous acid (HClO)-gated cascade signal amplification strategy precise miR-155 living cells, enabling accurate vivo ex detection This utilizes phosphorothioate (PT)-modified hairpin probe that is specifically deprotected by HClO uncaged miR-155, triggering catalytic assembly (CHA) to amplify fluorescence signals. The PT-CHA probes are encapsulated lipid nanoparticles (LNs), followed conjugating phosphatidylserine (PS)-binding peptide (PBP) selectively targeting intensity PT-CHA@LN-PBP aorta region shows clear differentiation among AS-bearing mice, miR-155-/- healthy mice. Moreover, strongly correlates plaque area progression can discriminate vulnerability risk under curve (AUC) 0.94. Imaging human aortic tissues further validates probe's capacity distinguish from normal endarterium. These findings establish as noninvasive, reliable diagnostic tool assessment AS.

Language: Английский

Citations

0

Structure-switching G-quadruplex: An efficient CRISPR/Cas12a signal reporter for label-free colorimetric biosensing DOI
Yang Chen, Bei Lv, Wenzhu Wang

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 307, P. 142410 - 142410

Published: March 22, 2025

Language: Английский

Citations

0

Integration of MicroRNAs with nanomedicine: tumor targeting and therapeutic approaches DOI Creative Commons
Pelin Telkoparan‐Akillilar, Silvia Chichiarelli, Paolo Tucci

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 7, 2025

MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a pivotal role in the post-transcriptional regulation of gene expression. Over past decade, they have emerged as key regulators cancer progression, influencing different cellular processes such proliferation, apoptosis, metastasis, and immune evasion. Their unique ability to target multiple genes simultaneously makes miRNAs highly attractive potential therapeutic agents oncology. However, several challenges hindered their direct clinical application, most notably inherent instability biological fluids, rapid degradation by nucleases, inefficient delivery specific tumor sites. Additionally, off-target effects for toxicity further complicate use miRNAs. Nanomedicine offers promising solution these enabling development advanced platforms stable, safe, targeted Nanoparticle-based systems, liposomes, polymeric nanoparticles, inorganic nanocarriers, can protect from degradation, improve bioavailability, allow precise targeting through passive or active mechanisms. These nanocarriers also be engineered release response stimuli within microenvironment, enhancing efficacy while minimizing side effects. This review will explore integration with nanotechnology, focusing on various nanoparticle formulations roles miRNA stability, specificity, function treatment. In addition, we discuss current advances preclinical applications, highlight tumor-targeting strategies, address remaining toxicity, immunogenicity, scalability. Future research should focus overcoming barriers, ultimately paving way widespread adoption personalized miRNA-based nanomedicine therapy.

Language: Английский

Citations

0

Phosphorothioate-Modified Hairpin G-Triplex Reporter-Assisted Split CRISPR/Cas12a-Powered Biosensor for “Turn-On” Fluorescent Detection of Nucleic Acid and Non-Nucleic Acid Targets DOI
Kai Shi,

Wenjie Luo,

Ying Cheng

et al.

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

CRISPR/Cas12a-powered biosensors with guanine (G)-rich sequence reporters (e.g., G-quadruplex and G-triplex) are widely used in detection applications due to their simplicity sensitivity. However, when these employed for molecular complex samples, they may encounter difficulties such as high background signal susceptibility interference because of the "turn-off" output. Herein, we explore, first time, a set phosphorothioate (ps)-modified (G4) G-triplex (G3) sequences that can bind thioflavin T (ThT) an active split CRISPR/Cas12a system (SCas12a) generate "turn-on" fluorescent signal. To apply this new phenomenon, develop universal SCas12a-powered biosensor nucleic acid (miRNA-21) non-nucleic (kanamycin) targets by using ps-modified hairpin G3 reporter (SCas12a/psHG3). Target recognition activates SCas12a's trans-cleavage activity, leading cleavage at loop region psHG3 reporter. The released prelocked psG3 DNA binds ThT produce strong fluorescence Without preamplification, strategy detect miRNA-21 limit 100 fM. Moreover, SCas12a/psHG3 was further utilized detecting kanamycin incorporating its aptamers, enabling concentrations low pM. This work is system, showcasing improved performance wide range synthetic biology-based sensing technology.

Language: Английский

Citations

0

Upgraded circular single-stranded DNA regulators for multiple-input multiple-output gene circuits in mammalian cells DOI Creative Commons
Linlin Tang, Jinghao Wang, Kaiqi Xu

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(20)

Published: May 16, 2025

Synthetic gene networks hold promise for genetic diagnostics and therapy but face limitations due to insufficient molecular tools. Gene-encoded circular single-stranded DNA (Css DNA) has been developed as a switchable vector enrich regulatory components beyond protein/RNA-based systems in mammalian cells. However, the previous Css regulator suffered from constrained sequence flexibility, disability of multiple-input multiple-output (MIMO) signals, lack endogenous orthogonal regulation. Here, we address these challenges by engineering “bridge” design into regulator. These bridges function sequence-programmable switches control expression, responding signals (such ATP, APE1, RNase H) enabling trans-regulation within or between DNAs. We exploit orthogonality construct three-input three-output circuits. The upgraded DNA–based strategy represents versatile powerful platform regulation provides promising avenue development synthetic networks.

Language: Английский

Citations

0

Random Sanitization in DNA Information Storage Using CRISPR-Cas12a DOI
Hongyu Shen, Zhi Weng, Haipei Zhao

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

DNA information storage provides an excellent solution for metadata due to its high density, programmability, and long-term stability. However, current research primarily focuses on the processes of storing reading data, lacking comprehensive solutions secure wiping. Herein, we present a method random sanitization in using CRISPR-Cas12a (RSDISC) based precise control thermodynamic energy primer-template hybridization. We utilize collateral cleavage (trans-activity) single-stranded (ssDNA) by achieve selective files metadata. This enables ssDNA degradation with different GC contents, lengths, secondary structures efficiency up 99.9% 28,258 oligonucleotides within one round. demonstrate that number erasable could reach 10

Language: Английский

Citations

2