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Biochemistry. Biokhimiia Jan 2024Nucleic acids (NAs) are important components of living organisms responsible for the storage and transmission of hereditary information. They form complex structures... (Review)
Review
Nucleic acids (NAs) are important components of living organisms responsible for the storage and transmission of hereditary information. They form complex structures that can self-assemble and bind to various biological molecules. DNAzymes are NAs capable of performing simple chemical reactions, which makes them potentially useful elements for creating DNA nanomachines with required functions. This review focuses on multicomponent DNA-based nanomachines, in particular on DNAzymes as their main functional elements, as well as on the structure of DNAzyme nanomachines and their application in the diagnostics and treatment of diseases. The article also discusses the advantages and disadvantages of DNAzyme-based nanomachines and prospects for their future applications. The review provides information about new technologies and the possibilities of using NAs in medicine.
Topics: DNA, Catalytic; DNA; Biosensing Techniques
PubMed: 38621754
DOI: 10.1134/S0006297924140141 -
ACS Applied Bio Materials Aug 2023The analysis and improvement of DNA nanostructure biostability is one of the keys areas of progress needed in DNA nanotechnology applications. Here, we present a...
The analysis and improvement of DNA nanostructure biostability is one of the keys areas of progress needed in DNA nanotechnology applications. Here, we present a plate-compatible fluorometric assay for measuring DNA nanostructure biostability using the common intercalator ethidium bromide. We demonstrate the assay by testing the biostability of duplex DNA, a double crossover DNA motif, and a DNA origami nanostructure against different nucleases and in fetal bovine serum. This method scales well to measure a large number of samples using a plate reader and can complement existing methods for assessing and developing robust DNA nanostructures.
Topics: DNA; Fluorometry; Nanostructures; Deoxyribonucleases
PubMed: 37262927
DOI: 10.1021/acsabm.3c00287 -
Advanced Materials (Deerfield Beach,... Sep 2023Controversy over artwork's authenticity is ongoing despite numerous technologies for copyright protection. Artists should build their own ways to protect the authority,...
Controversy over artwork's authenticity is ongoing despite numerous technologies for copyright protection. Artists should build their own ways to protect the authority, but these are still open to piracy. Here, a platform is proposed for developing anticounterfeiting labels based on physical unclonable functions (PUFs), in an artist-friendly manner, brushstrokes. Deoxyribonucleic acid (DNA), which is natural, biocompatible, and eco-friendly, can be applied as a paint that shows entropy-driven buckling instability of the liquid crystal phase. Brushed and wholly dried DNA exhibits line-shaped zig-zag textures with inherent randomness as a source of the PUF, and its primary performance and reliability are systematically examined. This breakthrough enables the utilization of these drawings in a wider range of applications.
Topics: Reproducibility of Results; Entropy; Liquid Crystals; DNA
PubMed: 37145961
DOI: 10.1002/adma.202302135 -
Nature Jan 2024Gene expression is regulated by transcription factors that work together to read cis-regulatory DNA sequences. The 'cis-regulatory code' - how cells interpret DNA... (Review)
Review
Gene expression is regulated by transcription factors that work together to read cis-regulatory DNA sequences. The 'cis-regulatory code' - how cells interpret DNA sequences to determine when, where and how much genes should be expressed - has proven to be exceedingly complex. Recently, advances in the scale and resolution of functional genomics assays and machine learning have enabled substantial progress towards deciphering this code. However, the cis-regulatory code will probably never be solved if models are trained only on genomic sequences; regions of homology can easily lead to overestimation of predictive performance, and our genome is too short and has insufficient sequence diversity to learn all relevant parameters. Fortunately, randomly synthesized DNA sequences enable testing a far larger sequence space than exists in our genomes, and designed DNA sequences enable targeted queries to maximally improve the models. As the same biochemical principles are used to interpret DNA regardless of its source, models trained on these synthetic data can predict genomic activity, often better than genome-trained models. Here we provide an outlook on the field, and propose a roadmap towards solving the cis-regulatory code by a combination of machine learning and massively parallel assays using synthetic DNA.
Topics: DNA; Genomics; Machine Learning; Regulatory Sequences, Nucleic Acid; Transcription Factors; Models, Genetic
PubMed: 38093018
DOI: 10.1038/s41586-023-06661-w -
Nature Structural & Molecular Biology Jul 2023Clustered regularly interspaced short palindromic repeats (CRISPR) sequences and CRISPR-associated (Cas) genes comprise CIRSPR-Cas effector complexes, which have...
Clustered regularly interspaced short palindromic repeats (CRISPR) sequences and CRISPR-associated (Cas) genes comprise CIRSPR-Cas effector complexes, which have revolutionized gene editing with their ability to target specific genomic loci using CRISPR RNA (crRNA) complementarity. Recognition of double-stranded DNA targets proceeds via DNA unwinding and base pairing between crRNA and the DNA target strand, forming an R-loop structure. Full R-loop extension is a prerequisite for subsequent DNA cleavage. However, the recognition of unintended sequences with multiple mismatches has limited therapeutic applications and is still poorly understood on a mechanistic level. Here we set up ultrafast DNA unwinding experiments on the basis of plasmonic DNA origami nanorotors to study R-loop formation by the Cascade effector complex in real time, close to base-pair resolution. We resolve a weak global downhill bias of the forming R-loop, followed by a steep uphill bias for the final base pairs. We also show that the energy landscape is modulated by base flips and mismatches. These findings suggest that Cascade-mediated R-loop formation occurs on short timescales in submillisecond single base-pair steps, but on longer timescales in six base-pair intermediate steps, in agreement with the structural periodicity of the crRNA-DNA hybrid.
Topics: R-Loop Structures; CRISPR-Cas Systems; RNA; DNA; Base Pairing; CRISPR-Associated Proteins
PubMed: 37415009
DOI: 10.1038/s41594-023-01019-2 -
Nature Materials Mar 2024In principle, designing and synthesizing almost any class of colloidal crystal is possible. Nonetheless, the deliberate and rational formation of colloidal quasicrystals...
In principle, designing and synthesizing almost any class of colloidal crystal is possible. Nonetheless, the deliberate and rational formation of colloidal quasicrystals has been difficult to achieve. Here we describe the assembly of colloidal quasicrystals by exploiting the geometry of nanoscale decahedra and the programmable bonding characteristics of DNA immobilized on their facets. This process is enthalpy-driven, works over a range of particle sizes and DNA lengths, and is made possible by the energetic preference of the system to maximize DNA duplex formation and favour facet alignment, generating local five- and six-coordinated motifs. This class of axial structures is defined by a square-triangle tiling with rhombus defects and successive on-average quasiperiodic layers exhibiting stacking disorder which provides the entropy necessary for thermodynamic stability. Taken together, these results establish an engineering milestone in the deliberate design of programmable matter.
Topics: DNA; Thermodynamics
PubMed: 37919350
DOI: 10.1038/s41563-023-01706-x -
Gene Oct 2023The potential of cells to guide their genome and configure genes to express at a given time and in response to specific stimuli is pivotal to regulate cellular processes... (Review)
Review
The potential of cells to guide their genome and configure genes to express at a given time and in response to specific stimuli is pivotal to regulate cellular processes such as tissue differentiation, organogenesis, organismal development, homeostasis, and disease. In this review, we focus on the diverse mechanisms involved in DNA replication and its degradation, mRNA synthesis, and associated regulation such as RNA capping, splicing, tailing, and export. mRNA turnover including Decapping, deadenylation, RNA interference, and Nonsense mediated mRNA decay followed by protein translation, post-translational modification, and protein turnover. We highlight recent advances in understanding the complex series of molecular mechanisms responsible for the remarkable cellular regulatory mechanisms.
Topics: Proteins; DNA; RNA; Protein Biosynthesis; Transcription, Genetic; RNA Splicing; RNA Stability
PubMed: 37506987
DOI: 10.1016/j.gene.2023.147672 -
Small (Weinheim An Der Bergstrasse,... Sep 2023Social biotic colonies often perform intricate tasks by interindividual communication and cooperation. Inspired by these biotic behaviors, a DNA nanodevice community is...
Social biotic colonies often perform intricate tasks by interindividual communication and cooperation. Inspired by these biotic behaviors, a DNA nanodevice community is proposed as a universal and scalable platform. The modular nanodevice as the infrastructure of platform contains a DNA origami triangular prism framework and a hairpin-swing arm machinery core. By coding and decoding a signal domain on the shuttled output strand in different nanodevices, an orthogonal inter-nanodevice communication network is established to connect multi-nanodevices into a functional platform. The nanodevice platform enables implementation of diverse tasks, including signal cascading and feedback, molecular input recording, distributed logic computing, and modeling of simulation for virus transmission. The nanodevice platform with powerful compatibility and programmability presents an elegant example of the combination of the distributed operation of multiple devices and the complicated interdevice communication network, and may become a new generation of intelligent DNA nanosystems.
Topics: DNA; Logic
PubMed: 37140089
DOI: 10.1002/smll.202302301 -
Genes Mar 2024The polymerase chain reaction (PCR) has played a fundamental role in our understanding of the world, and has applications across a broad range of disciplines. The... (Review)
Review
The polymerase chain reaction (PCR) has played a fundamental role in our understanding of the world, and has applications across a broad range of disciplines. The introduction of PCR into forensic science marked the beginning of a new era of DNA profiling. This era has pushed PCR to its limits and allowed genetic data to be generated from trace DNA. Trace samples contain very small amounts of degraded DNA associated with inhibitory compounds and ions. Despite significant development in the PCR process since it was first introduced, the challenges of profiling inhibited and degraded samples remain. This review examines the evolution of the PCR from its inception in the 1980s, through to its current application in forensic science. The driving factors behind PCR evolution for DNA profiling are discussed along with a critical comparison of cycling conditions used in commercial PCR kits. Newer PCR methods that are currently used in forensic practice and beyond are examined, and possible future directions of PCR for DNA profiling are evaluated.
Topics: Humans; Polymerase Chain Reaction; Forensic Sciences; DNA Fingerprinting; DNA; Forensic Genetics
PubMed: 38674373
DOI: 10.3390/genes15040438 -
Biosensors & Bioelectronics Oct 2023Deoxyribonucleic acid (DNA) is a carrier of genetic information. DNA hybridization is characterized by predictability, diversity, and specificity owing to the strict... (Review)
Review
Deoxyribonucleic acid (DNA) is a carrier of genetic information. DNA hybridization is characterized by predictability, diversity, and specificity owing to the strict complementary base-pairing assembly mode, which stimulates the use of DNA to build a variety of nanomachines, including DNA tweezers, motors, walkers, and robots. DNA nanomachines have become prevalent for signal amplification and transformation in the field of biosensing, providing a new method for constructing highly sensitive sensing analysis strategies. DNA tweezers have exhibited unique advantages in biosensing applications owing to their simple structures and fast responses. The two-state conformation of DNA tweezers, the open and closed states, enable them to open and close autonomously after stimulation, thus facilitating the quick detection of corresponding signal changes of different targets. This review discusses the recent progress in the application of DNA nanotweezers in the field of biosensing, and the trends in their development for application in the field of biosensing are summarized.
Topics: DNA; Biosensing Techniques; Nucleic Acid Hybridization; Nucleic Acid Conformation
PubMed: 37421799
DOI: 10.1016/j.bios.2023.115445