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Biotechnology Journal Jan 2020DNA nanotechnology is a new frontier in the field of tumor biotherapy. Simple DNA strands can be precisely constructed for integration into nanostructures of desired... (Review)
Review
DNA nanotechnology is a new frontier in the field of tumor biotherapy. Simple DNA strands can be precisely constructed for integration into nanostructures of desired shapes and sizes, with excellent stability and biocompatibility. In this review, an account of the wide range of nanostructures composed of DNA sequences and related advances in oncotherapy using aptamers and chemical drugs is given. Functional ligands, including enzymes, antibodies, and agents, have been appended to DNA frameworks based on their external and internal modifiability. Hence, additional functionalities, such as immunogenicity and enzymatic activity, have been obtained, which extend their practical applications. Importantly, aptamers and drugs can be attached to or incorporated into the wireframes, bringing in highly selective targeting and killing abilities for the modified DNA nanostructures (DNs). In conclusion, distinct DNA sequences, various functional molecules, and different interactions and modifications lead to the diversity of DNs. Currently, one of the leading areas is their applications in tumor therapy. But beyond that, DNs should have much wider application prospects.
Topics: Animals; Aptamers, Nucleotide; DNA; Humans; Mice; Nanomedicine; Nanostructures; Neoplasms
PubMed: 31464361
DOI: 10.1002/biot.201900094 -
Alimentary Pharmacology & Therapeutics Nov 2023Hepatitis B surface antigen (HBsAg) seroclearance marks regression of hepatitis B virus (HBV) infection. However, more than one-fifth of patients with functional cure...
BACKGROUND
Hepatitis B surface antigen (HBsAg) seroclearance marks regression of hepatitis B virus (HBV) infection. However, more than one-fifth of patients with functional cure following pegylated interferon-based therapy may experience HBsAg seroreversion. The mechanisms causing the HBV relapse remain unclear.
AIM
To investigate the level and origin of HBV transcripts in patients with functional cure and their role in predicting relapse.
METHODS
Liver tissue obtained from patients with functional cure, as well as uncured and treatment-naïve HBeAg-negative patients with chronic hepatitis B (CHB) were analysed for intrahepatic HBV markers. HBV capture and RNA sequencing were used to detect HBV integration and chimeric transcripts.
RESULTS
Covalently closed circular DNA (cccDNA) levels and the proportion of HBsAg-positive hepatocytes in functionally cured patients were significantly lower than those in uncured and treatment-naïve HBeAg-negative patients. Integrated HBV DNA and chimeric transcripts declined in functionally cured patients compared to uncured patients. HBsAg-positive hepatocytes present in 25.5% of functionally cured patients, while intrahepatic HBV RNA remained in 72.2%. The levels of intrahepatic HBV RNA, integrated HBV DNA, and chimeric transcripts were higher in functionally cured patients with intrahepatic HBsAg than in those without. The residual intrahepatic HBsAg in functionally cured patients was mainly derived from transcriptionally active integrated HBV DNA; meanwhile, trace transcriptional activity of cccDNA could also remain. Two out of four functionally cured patients with intrahepatic HBsAg and trace active cccDNA experienced HBV relapse.
CONCLUSION
Integrated HBV DNA and cccDNA maintain transcriptional activity and maybe involved in HBsAg seroreversion in intrahepatic HBsAg-positive patients with functional cure and linked to virological relapse.
Topics: Humans; Hepatitis B Surface Antigens; DNA, Viral; DNA, Circular; Hepatitis B e Antigens; Antiviral Agents; Hepatitis B virus; Hepatitis B, Chronic; Liver; RNA; Recurrence
PubMed: 37644711
DOI: 10.1111/apt.17670 -
Methods in Molecular Biology (Clifton,... 2024The use of DNA has helped to improve and speed up species identification and delimitation. However, it also provides new challenges to taxonomists. Incongruence of...
The use of DNA has helped to improve and speed up species identification and delimitation. However, it also provides new challenges to taxonomists. Incongruence of outcome from various markers and delimitation methods, bias from sampling and skewed species distribution, implemented models, and the choice of methods/priors may mislead results and also may, in conclusion, increase elements of subjectivity in species taxonomy. The lack of direct diagnostic outcome from most contemporary molecular delimitation approaches and the need for a reference to existing and best sampled trait reference systems reveal the need for refining the criteria of species diagnosis and diagnosability in the current framework of nomenclature codes and good practices to avoid nomenclatorial instability, parallel taxonomies, and consequently more and new taxonomic impediment.
Topics: DNA; DNA Barcoding, Taxonomic; Classification; Phylogeny; Species Specificity
PubMed: 38683310
DOI: 10.1007/978-1-0716-3581-0_2 -
Nature Oct 2023The past decades have witnessed the evolution of electronic and photonic integrated circuits, from application specific to programmable. Although liquid-phase DNA...
The past decades have witnessed the evolution of electronic and photonic integrated circuits, from application specific to programmable. Although liquid-phase DNA circuitry holds the potential for massive parallelism in the encoding and execution of algorithms, the development of general-purpose DNA integrated circuits (DICs) has yet to be explored. Here we demonstrate a DIC system by integration of multilayer DNA-based programmable gate arrays (DPGAs). We find that the use of generic single-stranded oligonucleotides as a uniform transmission signal can reliably integrate large-scale DICs with minimal leakage and high fidelity for general-purpose computing. Reconfiguration of a single DPGA with 24 addressable dual-rail gates can be programmed with wiring instructions to implement over 100 billion distinct circuits. Furthermore, to control the intrinsically random collision of molecules, we designed DNA origami registers to provide the directionality for asynchronous execution of cascaded DPGAs. We exemplify this by a quadratic equation-solving DIC assembled with three layers of cascade DPGAs comprising 30 logic gates with around 500 DNA strands. We further show that integration of a DPGA with an analog-to-digital converter can classify disease-related microRNAs. The ability to integrate large-scale DPGA networks without apparent signal attenuation marks a key step towards general-purpose DNA computing.
Topics: Algorithms; DNA; Oligonucleotides; Computers, Molecular; MicroRNAs; Disease
PubMed: 37704731
DOI: 10.1038/s41586-023-06484-9 -
Bioconjugate Chemistry Jan 2023Over the past 40 years, structural and dynamic DNA nanotechnologies have undoubtedly demonstrated to be effective means for organizing matter at the nanoscale and... (Review)
Review
Over the past 40 years, structural and dynamic DNA nanotechnologies have undoubtedly demonstrated to be effective means for organizing matter at the nanoscale and reconfiguring equilibrium structures, in a predictable fashion and with an accuracy of a few nanometers. Recently, novel concepts and methodologies have been developed to integrate nonequilibrium dynamics into DNA nanostructures, opening the way to the construction of synthetic materials that can adapt to environmental changes and thus acquire new properties. In this Review, we summarize the strategies currently applied for the construction of synthetic DNA filaments and conclude by reporting some recent and most relevant examples of DNA filaments that can emulate typical structural and dynamic features of the cytoskeleton, such as compartmentalization in cell-like vesicles, support for active transport of cargos, sustained or transient growth, and responsiveness to external stimuli.
Topics: Cytoskeleton; Nanotechnology; Nanostructures; Microtubules; DNA
PubMed: 36174970
DOI: 10.1021/acs.bioconjchem.2c00312 -
Advanced Drug Delivery Reviews Jul 2019Nanomaterials employed for enhanced drug delivery and therapeutic effects have been extensively investigated in the past decade. The outcome of current anticancer... (Review)
Review
Nanomaterials employed for enhanced drug delivery and therapeutic effects have been extensively investigated in the past decade. The outcome of current anticancer treatments based on conventional nanoparticles is suboptimal, due to the lack of biocompatibility, the deficient tumor targeting, the limited drug accumulation in the diseased region, etc. Alternatively, DNA-based nanocarriers have emerged as a novel and versatile platform to integrate the advantages of nanotechnologies and biological sciences, which shows great promise in addressing the key issues for biomedical studies. Rather than a genetic information carrier, DNA molecules can work as building blocks to fabricate programmable and bio-functional nanostructures based on Watson Crick base-pairing rules. The DNA-based materials have demonstrated unique properties, such as uniform sizes and shapes, pre-designable and programmable nanostructures, site-specific surface functionality and excellent biocompatibility. These intrigue features allow DNA nanostructures to carry functional moieties to realize precise tumor recognition, customized therapeutic functions and stimuli-responsive drug release, making them highly attractive in many aspects of cancer treatment. In this review, we focus on the recent progress in DNA-based self-assembled materials for the biomedical applications, such as molecular imaging, drug delivery for in vitro or in vivo cancer treatments. We introduce the general strategies and essential requirements for fabricating DNA-based nanocarriers. We summarize the advances of DNA-based nanocarriers according to their functionalities and structural properties for cancer diagnosis and therapy. Finally, we discuss the challenges and future perspectives regarding the detailed in vivo parameters of DNA materials and the design of intelligent DNA nanomedicine for individualized cancer therapy.
Topics: Animals; DNA; Drug Carriers; Humans; Nanostructures; Neoplasms
PubMed: 30769047
DOI: 10.1016/j.addr.2019.02.003 -
Topics in Current Chemistry (Cham) Apr 2020Cellular functions rely on a series of organized and regulated multienzyme cascade reactions. The catalytic efficiencies of these cascades depend on the precise spatial... (Review)
Review
Cellular functions rely on a series of organized and regulated multienzyme cascade reactions. The catalytic efficiencies of these cascades depend on the precise spatial organization of the constituent enzymes, which is optimized to facilitate substrate transport and regulate activities. Mimicry of this organization in a non-living, artificial system would be very useful in a broad range of applications-with impacts on both the scientific community and society at large. Self-assembled DNA nanostructures are promising applications to organize biomolecular components into prescribed, multidimensional patterns. In this review, we focus on recent progress in the field of DNA-scaffolded assembly and confinement of multienzyme reactions. DNA self-assembly is exploited to build spatially organized multienzyme cascades with control over their relative distance, substrate diffusion paths, compartmentalization and activity actuation. The combination of addressable DNA assembly and multienzyme cascades can deliver breakthroughs toward the engineering of novel synthetic and biomimetic reactors.
Topics: DNA; Enzymes; Protein Engineering
PubMed: 32248317
DOI: 10.1007/s41061-020-0299-3 -
Physical Chemistry Chemical Physics :... Jun 2023DNA's charge transfer and self-assembly characteristics have made it a hallmark of molecular electronics for the past two decades. A fast and efficient charge transfer...
DNA's charge transfer and self-assembly characteristics have made it a hallmark of molecular electronics for the past two decades. A fast and efficient charge transfer mechanism with programmable properties using DNA nanostructures is required for DNA-based nanoelectronic applications and devices. The ability to integrate DNA with inorganic substrates becomes critical in this process. Such integrations may affect the conformation of DNA, altering its charge transport properties. Thus, using molecular dynamics simulations and first-principles calculations in conjunction with Green's function approach, we explore the impact of the Au (111) substrate on the conformation of DNA and analyze its effect on the charge transport. Our results indicate that DNA sequence, leading to its molecular conformation on the Au substrate, is critical to engineer charge transport properties. We demonstrate that DNA fluctuates on a gold substrate, sampling various distinct conformations over time. The energy levels, spatial locations of molecular orbitals and the DNA/Au contact atoms can differ between these distinct conformations. Depending on the sequence, at the HOMO, the charge transmission differs up to 60 times between the top ten conformations. We demonstrate that the relative positions of the nucleobases are critical in determining the conformations and the coupling between orbitals. We anticipate that these results can be extended to other inorganic surfaces and pave the way for understanding DNA-inorganic interface interactions for future DNA-based electronic device applications.
Topics: Nanostructures; Gold; Molecular Conformation; DNA; Electronics
PubMed: 37309195
DOI: 10.1039/d2cp05009a -
Trends in Biochemical Sciences Nov 2021Single-molecule localization microscopy (SMLM) is a potent tool to examine biological systems with unprecedented resolution, enabling the investigation of increasingly... (Review)
Review
Single-molecule localization microscopy (SMLM) is a potent tool to examine biological systems with unprecedented resolution, enabling the investigation of increasingly smaller structures. At the forefront of these developments is DNA-based point accumulation for imaging in nanoscale topography (DNA-PAINT), which exploits the stochastic and transient binding of fluorescently labeled DNA probes. In its early stages the implementation of DNA-PAINT was burdened by low-throughput, excessive acquisition time, and difficult integration with live-cell imaging. However, recent advances are addressing these challenges and expanding the range of applications of DNA-PAINT. We review the current state of the art of DNA-PAINT in light of these advances and contemplate what further developments remain indispensable to realize live-cell imaging.
Topics: DNA; Microscopy, Fluorescence; Single Molecule Imaging
PubMed: 34247944
DOI: 10.1016/j.tibs.2021.05.010 -
Ageing Research Reviews Dec 2022Cellular changes that are linked to aging in humans include genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, cellular... (Review)
Review
Cellular changes that are linked to aging in humans include genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, cellular senescence, and altered intercellular communications. The extent of the changes in these aging hallmarks and their interactions with each other are part of the human aging. However, the molecular mechanisms through which the aging hallmarks interact with each other remain unclear. Studies have indicated a potential role for the type I interferon (IFN) and p53-inducible IFI16 proteins in interactions with the aging hallmarks. The IFI16 proteins are members of the PYHIN protein family. Proteins in the family share a DNA-binding domain (the HIN domain) and a protein-protein interaction pyrin domain (PYD). IFI16 proteins are needed for cytosolic DNA-induced activation of the cGAS-STING pathway for type I IFN (IFN-β) expression. The pathway plays an important role in aging-related inflammation (inflammaging). Further, increased levels of the IFI16 proteins potentiate the cell growth inhibitory functions of the p53 and pRb tumor suppressors proteins. Moreover, IFI16 proteins are needed for most aging hallmarks. Therefore, here we discuss how an improved understanding of the role of the IFI16 proteins in integration of the aging hallmarks has potential to improve the human health and lifespan.
Topics: Humans; Tumor Suppressor Protein p53; Phosphoproteins; Cellular Senescence; Aging; DNA; Nuclear Proteins
PubMed: 36270606
DOI: 10.1016/j.arr.2022.101765