DNA "nano-claw": logic-based autonomous cancer targeting and therapy.
Ontology highlight
ABSTRACT:
SUBMITTER: You M
PROVIDER: S-EPMC3935767 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
Publications
DNA "nano-claw": logic-based autonomous cancer targeting and therapy.
You Mingxu M Peng Lu L Shao Na N Zhang Liqin L Qiu Liping L Cui Cheng C Tan Weihong W
Journal of the American Chemical Society 20140113 4
Cell types, both healthy and diseased, can be classified by inventories of their cell-surface markers. Programmable analysis of multiple markers would enable clinicians to develop a comprehensive disease profile, leading to more accurate diagnosis and intervention. As a first step to accomplish this, we have designed a DNA-based device, called "Nano-Claw". Combining the special structure-switching properties of DNA aptamers with toehold-mediated strand displacement reactions, this claw is capabl ...[more]
Similar Datasets
Project description:Many plants autonomously change morphology and function in response to environmental stimuli or sequences of stimuli. In contrast with the electronically-integrated sensors, actuators, and microprocessors in traditional mechatronic systems, natural systems embody these sensing, actuation, and control functions within their compositional and structural features. Inspired by nature, we embody logic in autonomous systems to enable them to respond to multiple stimuli. Using 3D printable fibrous composites, we fabricate structures with geometries near bifurcation points associated with a transition between bistability and monostability. When suitable stimuli are present, the materials swell anisotropically. This forces a key geometric parameter to pass through a bifurcation, triggering rapid and large-amplitude self-actuation. The actuation time can be programmed by varying structural parameters (from 0.6 to 108 s for millimeter-scale structures). We demonstrate this bioinspired control strategy with examples that respond to their environment according to their embodied logic, without electronics, external control, or tethering.
| S-EPMC6328580 | biostudies-literature
Project description:The specific inventory of molecules on diseased cell surfaces (e.g., cancer cells) provides clinicians an opportunity for accurate diagnosis and intervention. With the discovery of panels of cancer markers, carrying out analyses of multiple cell-surface markers is conceivable. As a trial to accomplish this, we have recently designed a DNA-based device that is capable of performing autonomous logic-based analysis of two or three cancer cell-surface markers. Combining the specific target-recognition properties of DNA aptamers with toehold-mediated strand displacement reactions, multicellular marker-based cancer analysis can be realized based on modular AND, OR, and NOT Boolean logic gates. Specifically, we report here a general approach for assembling these modular logic gates to execute programmable and higher-order profiling of multiple coexisting cell-surface markers, including several found on cancer cells, with the capacity to report a diagnostic signal and/or deliver targeted photodynamic therapy. The success of this strategy demonstrates the potential of DNA nanotechnology in facilitating targeted disease diagnosis and effective therapy.
| S-EPMC4308741 | biostudies-literature
Project description:Chemically or optically powered active matter plays an increasingly important role in materials design, but its computational potential has yet to be explored systematically. The competition between energy consumption and dissipation imposes stringent physical constraints on the information transport in active flow networks, facilitating global optimization strategies that are not well understood. Here, we combine insights from recent microbial experiments with concepts from lattice-field theory and non-equilibrium statistical mechanics to introduce a generic theoretical framework for active matter logic. Highlighting conceptual differences with classical and quantum computation, we demonstrate how the inherent non-locality of incompressible active flow networks can be utilized to construct universal logical operations, Fredkin gates and memory storage in set-reset latches through the synchronized self-organization of many individual network components. Our work lays the conceptual foundation for developing autonomous microfluidic transport devices driven by bacterial fluids, active liquid crystals or chemically engineered motile colloids.
| S-EPMC5414041 | biostudies-literature
Project description:DNA bio-computing is an emerging trend in modern science that is based on interactions among biomolecules. Special types of DNAs are aptamers that are capable of selectively forming complexes with target compounds. This review is devoted to a discussion of logic gates based on aptamers for the purposes of medicine and analytical chemistry. The review considers different approaches to the creation of logic gates and identifies the general algorithms of their creation, as well as describes the methods of obtaining an output signal which can be divided into optical and electrochemical. Aptameric logic gates based on DNA origami and DNA nanorobots are also shown. The information presented in this article can be useful when creating new logic gates using existing aptamers and aptamers that will be selected in the future.
| S-EPMC7700249 | biostudies-literature
Project description:Dysregulation or mutation of DNA binding proteins such as transcription factors (TFs) is associated with the onset and progression of various types of disease, including cancer. Alteration of TF activity occurs in numerous cancer tissues due to gene amplification, deletion, and point mutations, and epigenetic modification. Although cancer-associated TFs are promising targets for cancer therapy, development of drugs targeting these TFs has historically been difficult due to the lack of high-throughput screening methods. Recent advances in technology for identification and selective inhibition of DNA binding proteins enable cancer researchers to develop novel therapeutics targeting cancer-associated TFs. In the present review, we summarize known cancer-associated TFs according to cancer type and introduce recently developed high-throughput approaches to identify selective inhibitors of cancer-associated TFs.
| S-EPMC7156841 | biostudies-literature
Project description:Cancer chemotherapy and radiotherapy are designed to kill cancer cells mostly by inducing DNA damage. DNA damage is normally recognized and repaired by the intrinsic DNA damage response machinery. If the damaged lesions are successfully repaired, the cells will survive. In order to specifically and effectively kill cancer cells by therapies that induce DNA damage, it is important to take advantage of specific abnormalities in the DNA damage response machinery that are present in cancer cells but not in normal cells. Such properties of cancer cells can provide biomarkers or targets for sensitization. For example, defects or upregulation of the specific pathways that recognize or repair specific types of DNA damage can serve as biomarkers of favorable or poor response to therapies that induce such types of DNA damage. Inhibition of a DNA damage response pathway may enhance the therapeutic effects in combination with the DNA-damaging agents. Moreover, it may also be useful as a monotherapy when it achieves synthetic lethality, in which inhibition of a complementary DNA damage response pathway selectively kills cancer cells that have a defect in a particular DNA repair pathway. The most striking application of this strategy is the treatment of cancers deficient in homologous recombination by poly(ADP-ribose) polymerase inhibitors. In this review, we describe the impact of targeting the cancer-specific aberrations in the DNA damage response by explaining how these treatment strategies are currently being evaluated in preclinical or clinical trials.
| S-EPMC4317796 | biostudies-literature
Project description:MotivationA major goal of personalized medicine in oncology is the optimization of treatment strategies given measurements of the genetic and molecular profiles of cancer cells. To further our knowledge on drug sensitivity, machine learning techniques are commonly applied to cancer cell line panels.ResultsWe present a novel integer linear programming (ILP) formulation, called MEthod for Rule Identification with multi-omics DAta (MERIDA), for predicting the drug sensitivity of cancer cells. The method represents a modified version of the LOBICO method by Knijnenburg et al. and yields easily interpretable models amenable to a Boolean logic based interpretation. Since the proposed altered logical rules lead to an enormous acceleration of the running times of MERIDA compared to LOBICO, we can not only consider larger input feature sets integrated from genetic and molecular omics data but also build more comprehensive models that mirror the complexity of cancer initiation and progression. Moreover, we enable the inclusion of a priori knowledge that can either stem from biomarker databases or can also be newly acquired knowledge gathered iteratively by previous runs of MERIDA. Our results show that this approach does not only lead to an improved predictive performance but also identifies a variety of putative sensitivity and resistance biomarkers. We also compare our approach to state-of-the-art machine learning methods and demonstrate the superior performance of our method. Hence, MERIDA has great potential to deepen our understanding of the molecular mechanisms causing drug sensitivity or resistance.Availability and implementationThe corresponding code is available on github (https://github.com/unisb-bioinf/MERIDA.git).Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC8570817 | biostudies-literature
Project description:Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis. The activities of ICL agents, in particular platinum-based therapies, establish a "molecular landscape," i.e., a pattern of DNA damage that can potentially be further exploited therapeutically with DDR-targeting agents. If the molecular landscape created by platinum-based agents could be better defined at the molecular level, a systematic, mechanistic rationale(s) could be developed for the use of DDR-targeting therapies in combination/maintenance protocols for specific, clinically advanced malignancies. New therapeutic drugs such as poly(ADP-ribose) polymerase (PARP) inhibitors are examples of DDR-targeting therapies that could potentially increase the DNA damage and replication stress imposed by platinum-based agents in tumor cells and provide therapeutic benefit for patients with advanced malignancies. Recent studies have shown that the use of PARP inhibitors together with platinum-based agents is a promising therapy strategy for ovarian cancer patients with "BRCAness", i.e., a phenotypic characteristic of tumors that not only can involve loss-of-function mutations in either BRCA1 or BRCA2, but also encompasses the molecular features of BRCA-mutant tumors. On the basis of these promising results, additional mechanism-based studies focused on the use of various DDR-targeting therapies in combination with platinum-based agents should be considered. This review discusses, in general, (1) ICL agents, primarily platinum-based agents, that establish a molecular landscape that can be further exploited therapeutically; (2) multiple points of potential intervention after ICL agent-induced crosslinking that further predispose to cell death and can be incorporated into a systematic, therapeutic rationale for combination/ maintenance therapy using DDR-targeting agents; and (3) available agents that can be considered for use in combination/maintenance clinical protocols with platinum-based agents for patients with advanced malignancies.
| S-EPMC5471128 | biostudies-literature
Project description:Cancer is one of the most complex diseases that has resulted in multiple genetic disorders and cellular abnormalities. Globally, cancer is the most common health concern disease that is affecting human beings. Great efforts have been made over the past decades in biology with the aim of searching novel and more efficient tools in therapy. Thus, small interfering RNAs (siRNAs) have been considered one of the most noteworthy developments which are able to regulate gene expression following a process known as RNA interference (RNAi). RNAi is a post-transcriptional mechanism that involves the inhibition of gene expression through promoting cleavage on a specific area of a target messenger RNA (mRNA). This technology has shown promising therapeutic results for a good number of diseases, especially in cancer. However, siRNA therapeutics have to face important drawbacks in therapy including stability and successful siRNA delivery in vivo. In this regard, the development of effective siRNA delivery systems has helped addressing these issues by opening novel therapeutic windows which have allowed to build up important advances in Nanomedicine. In this review, we discuss the progress of siRNA therapy as well as its medical application via nanoparticle-mediated delivery for cancer treatment.
| S-EPMC6504672 | biostudies-literature
Project description:The utilization of photodynamic therapy (PDT) has been rapidly increasing due to its advantage as an effective treatment modality for cancer. The organic photosensitizers employed for PDT have some disadvantages, including high toxicity, non-selectivity toward tumors and poor absorption of light. The low light penetration into the tumor sites resulting from low wavelength of absorption and long-term skin photosensitivity. Hence, the attention toward non-toxic inorganic photosensitizers like noble metal nanoparticles (NPs) has been increasing nowadays. In bioscience, NPs are replacing organic dyes since they have photostability and non-toxicity. Generally, nanomaterials can easily form compounds with other substances as well as organic materials and the modified NPs surface enhances the chemical activity. Among the metal NPs, noble metals, especially gold and silver are attractive because of their size and shape-dependent unique optoelectronic properties. The coating of inorganic/organic materials on top of the noble metal makes the NPs bio-compatible and less toxic. Furthermore, Ag- and Au-based inorganic/organic complex NPs could offer a new possibility because of their unique structures. Meanwhile, the coating of inorganic/organic complex NPs protects the noble metals and stabilizes them against chemical corrosion and enhances the production of reactive oxygen species. Thus, in this review, we have highlighted the role of Ag- and Au-based inorganic/organic hybrid nano-photosensitizers in photodynamic therapy. Communicated by Ramaswamy H. Sarma.
| S-EPMC7232883 | biostudies-literature