Article
Biophysics
Wenchan Deng, Jing Yang Xu, Hanyong Peng, Cheng Zhi Huang, X. Chris Le, Hongquan Zhang
Summary: This study reports a toehold-exchange translator and translator-mediated DNAzyme motor systems that enable sensitive responses to various nucleic acid targets using the same DNAzyme motor without requiring redesign. The translator efficiently converts nucleic acid targets into specific output DNA, activating the DNAzyme motor and enabling autonomous movement. By adjusting the target-binding region of the translator, the same DNAzyme motor system can respond to multiple nucleic acid targets. The study also demonstrates the construction and operation of four logic gates using the translator and DNAzyme motor, enhancing the biosensing applications of DNA motors.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Biophysics
Yanmin Gao, Hongyan Qiao, Victor Pan, Zhaoguan Wang, Jiaojiao Li, Yanan Wei, Yonggang Ke, Hao Qi
Summary: In this study, a new approach for accurate genotyping of highly fragmented DNA was presented, with toehold-assisted padlock probe systems designed for 14 different single-nucleotide variants. By combining toehold-mediated strand displacement technology, precise genotyping of low concentration variant alleles in liquid biopsy samples was achieved, offering a new commercial approach for high-resolution genetic variation analysis.
BIOSENSORS & BIOELECTRONICS
(2021)
Article
Biochemical Research Methods
Roser Montagud-Martinez, Maria Heras-Hernandez, Lucas Goiriz, Jose-Antonio Daros, Guillermo Rodrigo
Summary: DNA nanotechnology and DNA computing have seen significant advancements over the past decade, resulting in a variety of functional stable structures and dynamic circuits. A new study utilized CRISPR-Cas systems to engineer logic circuits based on isothermal strand displacement, demonstrating good interoperability and expanding the repertoire of substrates and reactions for DNA computing.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Erica Del Grosso, Patrick Irmisch, Serena Gentile, Leonard J. Prins, Ralf Seidel, Francesco Ricci
Summary: This study presents a general approach to achieve dissipative control over toehold-mediated strand-displacement, a widely used reaction in DNA nanotechnology. By re-engineering the classic reaction, the high-energy invader strand is converted into a low-energy waste product, allowing the system to spontaneously return to its original state over time. This method enables unique temporal activation of DNA systems and is reversible and highly controllable.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Analytical
Minghao Hu, Ziyi Chu, Haitao Wang, Wenbo Zhao, Tongbo Wu
Summary: Strand replacement technology faces various and complex applications as a component in the DNA machine and DNA network. By modifying remote toehold-mediated strand displacement, we have enabled it to operate with asymmetric spacer and asymmetric responses to spacer hybridization. Moreover, we have discovered a series of unique modulations, which will expand the application scope of strand displacement technology.
MICROCHEMICAL JOURNAL
(2023)
Review
Biotechnology & Applied Microbiology
Sai Sumanjali Yarra, Ganapathy Ashok, Utpal Mohan
Summary: Toehold switches are newly designed riboregulators with two RNA components and linear-linear RNA interactions, providing regulation of gene expression. They are highly versatile, orthogonal, programmable, and find applications in various fields of synthetic biology.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Shaohua Xu, Yueliang Wang, Yuanyuan Yao, Lifen Chen, Jiahui Xu, Bin Qiu, Longhua Guo
Summary: This study proposed a highly sensitive strategy for miRNA-21 detection using programmable toehold-mediated strand displacement (TMSD) and dark-field microscopy imaging. The method achieved highly specific recognition and amplification of miRNA-21 through the hybridization of assist strands and substrate strand. By modifying glucose oxidase (Gox) on the assist strands, the size and scattering intensity of Au@Ag NCs were reduced, allowing for the quantitative detection of miRNA-21.
Article
Chemistry, Analytical
Yinping Deng, Jun Du, Donghua Chen, Guo-Jiang Mao, Bin Yang, Yin Zhang, Zhu Su, Hanfen Cai
Summary: A novel junction toehold with low signal leakage is reported in this study, which cooperatively and sequentially activates DNA strand displacement process by two inputs with independent oligonucleotide sequences, allowing kinetics to be flexibly tuned independently by multi-parameters.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Article
Biochemistry & Molecular Biology
You Wu, Wang Luo, Zhi Weng, Yongcan Guo, Hongyan Yu, Rong Zhao, Li Zhang, Jie Zhao, Dan Bai, Xi Zhou, Lin Song, Kena Chen, Junjie Li, Yujun Yang, Guoming Xie
Summary: CRISPR technology has achieved great breakthroughs and is becoming the most promising molecular tool. This research proposes a novel CRISPR/Cas12a activation mode to improve its performance and broaden its application boundaries, which eliminates the need for protospacer adjacent motif and accurately activates Cas12a through toehold-mediated strand displacement and branch migration.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Genetics & Heredity
Lihi Gershon, Martin Kupiec
Summary: Acetylation of lysine 56 on histone H3 in yeast is involved in processes affecting genome stability, particularly in DNA replication and repair. This modification occurs in the S-phase of the cell cycle to mark newly synthesized histones, but is removed by deacetylases in the G2/M phase to prevent genomic instability. The roles played by H3K56 acetylation and deacetylases Hst3 and Hst4 in maintaining genome stability are crucial but not fully understood.
Article
Physics, Multidisciplinary
Gal Ness, Andrea Alberti, Yoav Sagi
Summary: Quantum speed limits place constraints on the pace of state evolution. A new bound has been discovered for states with a bounded energy spectrum, which is dual to the existing Margolus-Levitin bound. This finding is relevant for quantum information applications.
PHYSICAL REVIEW LETTERS
(2022)
Article
Biophysics
Dan Bai, Xi Zhou, Wang Luo, Hongyan Yu, Shulian Bai, You Wu, Lin Song, Kena Chen, Yaxing Xie, Xueping Chen, Jie Zhao, Yixin Fu, Yujun Yang, Junjie Li, Guoming Xie
Summary: Nucleic acid nanotechnologies based on toehold-mediated strand displacement have shown great potential for detecting single-nucleotide variations (SNVs). In this study, a cooperative hybridization strategy relying on a dual-toehold and bulge-loop (DT & BL) probe, coupled with the strand displacement catalytic (SDC) cycle, was developed to improve the specificity and reaction rate. The feasibility of this platform was demonstrated by successfully identifying cancer-related genes and detecting clinical samples. This study offers a new perspective for constructing highly specific probes based on dynamic DNA nanotechnology, and provides a promising tool for clinical diagnostics.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Chemistry, Analytical
Yeru Wang, Yu Wang, Su Liu, Wenyu Sun, Manru Zhang, Long Jiang, Minghan Li, Jinghua Yu, Jiadong Huang
Summary: A smart tripedal DNA walker is designed in this research, which can move freely on the electrode with improved walking efficiency, eliminating the drawbacks of high cost and instability, showing potential in OTA detection applications.
ANALYTICA CHIMICA ACTA
(2021)
Article
Multidisciplinary Sciences
Chisato Terada, Kaho Oh, Ryutaro Tsubaki, Bun Chan, Nozomi Aibara, Kaname Ohyama, Masa-Aki Shibata, Takehiko Wada, Mariko Harada-Shiba, Asako Yamayoshi, Tsuyoshi Yamamoto
Summary: In this study, a toehold-bearing ASO architecture is developed to mitigate a broad spectrum of off-target interactions, significantly enhancing the safety profile of ASO drugs.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Tina Haagensen, Joshua L. Gaschk, Johanna T. Schultz, Christofer J. Clemente
Summary: Manoeuvrability is crucial for animals to rapidly change their direction of movement, and it depends on various factors such as lateral forces, friction, body rotation, and alignment with the new heading. This study analyzed high-speed turning in domestic dogs and found that maximum speed decreased with higher angular velocity, greater centripetal acceleration, and smaller turning radii. The study also revealed that body size and shape impact turning performance, with medium-sized dogs demonstrating better turning ability. These findings have important implications for understanding the relationship between form and function in animal locomotion and predicting predator-prey encounters.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Rajeev Yadav, Julia R. Widom, Adrien Chauvier, Nils G. Walter
Summary: This study used single molecule fluorescence technology to reveal three dynamically interconverting conformations of the fluoride riboswitch. Specifically, the fluoride ion snap-locks the conformation through its interaction with magnesium-induced RNA, and a long-range base pair plays a crucial role in the process. Additionally, the proximally paused RNA polymerase further promotes riboswitch docking. Finally, the study found that fluoride binding at short RNA lengths is an early step towards folding into the docked conformation.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Zi Li, Molly McNeely, Erin Sandford, Muneesh Tewari, Alexander Johnson-Buck, Nils G. Walter
Summary: From traditional enzyme-linked immunosorbent assay (ELISA) to modern next-generation sequencing, many sensitive and specific biomarker detection assays require capturing analytes at a surface. However, surface-based assays have limited capture efficiency from dilute solutions, resulting in detection sensitivity in the femtomolar-to-nanomolar range. To address this challenge, we use an aqueous two-phase system (ATPS) to concentrate target molecules near the assay surface, improving capture efficiency and achieving subfemtomolar detection limits without amplification. This approach enhances the sensitivity of surface-based assays by approximately 300-fold.
Article
Chemistry, Multidisciplinary
Aaron T. Blanchard, Zi Li, Elizabeth C. Duran, Catherine E. Scull, J. Damon Hoff, Keenan R. Wright, Victor Pan, Nils G. Walter
Summary: DNA-based FluoroCubes were developed as a solution to photobleaching in fluorescence microscopy. These compact FluoroCubes, coupled with up to 6 fluorescent dyes, exhibit enhanced photostability up to 50 times and emit a higher number of photons up to 40 times compared to single dyes. The study addresses the mechanism behind the improved photostability and confirms the compatibility of FluoroCubes with FRET and dark quenching applications.
Article
Biochemistry & Molecular Biology
Sujay Ray, Shiba S. Dandpat, Surajit Chatterjee, Nils G. Walter
Summary: The noncoding, structured 5'-untranslated regions (5'-UTRs) of bacterial mRNAs can regulate translation efficiency through the formation of structures that interact with the ribosome. This study investigates how the binding of a small ligand controls the recruitment and dissociation of the bacterial ribosome to the Shine-Dalgarno sequence. It is found that ligand binding stabilizes the riboswitch structure, which both inhibits ribosome recruitment and accelerates ribosome dissociation. The proximity of the 5'-UTR and the stability of the SD:anti-SD interaction play important roles in modulating the initial ribosome-mRNA interaction.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biophysics
Tanmay Chatterjee, Alexander Johnson-Buck, Nils G. Walter
Summary: Sensitive assays of protein biomarkers play a critical role in clinical diagnostics and biomedical research. Nucleic acid aptamers generated by SELEX have shown promise as an alternative to immunoreagents for detection, offering advantages in synthesis and reproducibility. SiMREPS, a single molecule recognition platform, allows for high sensitivity detection of biomarkers without requiring high-affinity probes. This study demonstrates the applicability of aptamers as detection probes in SiMREPS for two clinically relevant biomarkers, VEGF165 and IL-8, with detection limits in the low femtomolar range.
BIOSENSORS & BIOELECTRONICS
(2022)
Correction
Chemistry, Multidisciplinary
Aaron T. Blanchard, Zi Li, Elizabeth C. Duran, Catherine E. Scull, J. Damon Hoff, Keenan R. Wright, Victor Pan, Nils G. Walter
Article
Biochemistry & Molecular Biology
Adrien Chauvier, Jason C. C. Porta, Indrajit Deb, Emily Ellinger, Katarina Meze, Aaron T. T. Frank, Melanie D. D. Ohi, Nils G. G. Walter
Summary: This study investigates the interaction between RNA polymerase and nascent transcripts during transcription. It is found that the transcription process of a preQ(1) riboswitch can be modulated by the RNA polymerase and the conformation of the nascent RNA. Ligand binding to the riboswitch leads to the release of RNA polymerase pause and the continuation of transcription. The mechanism by which riboswitch folding modulates pausing is revealed through cryo-electron microscopy reconstructions.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Elizabeth Duran, Andreas Schmidt, Robb Welty, Ameya P. Jalihal, Sethuramasundaram Pitchiaya, Nils G. Walter
Summary: Cellular machineries that drive gene expression and regulate it rely on the assembly and interactions of proteins and RNA called ribonucleoprotein complexes (RNPs). Recreating these cellular machines and understanding their mechanisms is challenging. Single molecule fluorescence microscopy studies within crude or recombinantly supplemented cell extracts can provide insights into the behavior of specific biomolecules within RNPs in native cellular environments. This review discusses the methods and strategies used in dissecting RNP-driven processes, with a focus on pre-mRNA splicing and transcription regulation.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2023)
Article
Pharmacology & Pharmacy
Emily Ellinger, Adrien Chauvier, Rosa A. Romero, Yichen Liu, Sujay Ray, Nils G. Walter
Summary: This review examines the potential of riboswitches as novel antibacterial drug targets. The limited mechanisms of action of currently available antibiotics are summarized, followed by a delineation of the functional mechanisms of riboswitches. The potential for developing novel approaches that target paradigmatic riboswitches in the context of their bacterial gene expression machinery is discussed.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Article
Chemistry, Physical
Guoming Gao, Nils G. Walter
Summary: Biomolecular condensates are membraneless cellular compartments formed by phase separation, which play crucial roles in regulating cellular functions. Live-cell single particle tracking has revealed the mesoscopic organization and biological functions of condensates. However, there is a lack of quantitative benchmarking and objective comparison of boundary detection methods for condensates. In this study, synthetic data with defined ground truth is used to evaluate the most commonly used methods for condensate boundary detection, providing guidance for selecting optimal methods in imaging-based studies of condensates.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Nanoscience & Nanotechnology
Mathias Centola, Erik Poppleton, Sujay Ray, Martin Centola, Robb Welty, Julian Valero, Nils G. Walter, Petr Sulc, Michael Famulok
Summary: Molecular engineering aims to design nanoassemblies for complex tasks, but efficient chemical-fuel-driven nanoscale driver-follower systems have not been realized. In this study, a DNA nanomachine driven by the chemical energy of DNA-templated RNA-transcription-consuming nucleoside triphosphates was developed, generating rhythmic pulsating motion and successfully coupling with a passive follower.
NATURE NANOTECHNOLOGY
(2023)
Review
Urology & Nephrology
Guoming Gao, Emily S. Sumrall, Sethuramasundaram Pitchiaya, Markus Bitzer, Simon Alberti, Nils G. Walter
Summary: The regulation of solute microenvironments is crucial for cellular homeostasis. In the kidney, biomolecular condensates formed through hyperosmotic phase separation play important roles in kidney physiology and disease.
NATURE REVIEWS NEPHROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Qian Hou, Surajit Chatterjee, Paul E. Lund, Krishna C. Suddala, Nils G. Walter
Summary: This study investigates the thermodynamic and kinetic folding properties of two riboswitches from different bacteria and the effects of urea and trimethylamine N-oxide (TMAO) on their folding. The results show that the riboswitch from a thermophilic bacterium is more thermotolerant and that urea destabilizes their folded structure while TMAO counteracts urea denaturation. These findings shed light on how subtle sequence adaptations in a thermophilic bacterium can stabilize a common RNA structure.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Rebecca T. Perelman, Andreas Schmidt, Umar Khan, Nils G. Walter
Summary: This study investigates the spatial localization and diffusion of mRNA in cellular ribonucleoprotein (RNP) granules. The results show that mRNA molecules are often localized at the boundaries of these granules, potentially due to intermolecular interactions.
