A DNA-Based Nanocarrier for Efficient Gene Delivery and Combined Cancer Therapy

The efficient delivery of a therapeutic gene into target tissues has remained a major obstacle in realizing a viable gene-based medicine. Herein, we introduce a facile and universal strategy to construct a DNA nanostructure-based codelivery system containing a linear tumor therapeutic gene (p53) and a chemotherapeutic drug (doxorubicin, DOX) for combined therapy of multidrug resistant tumor (MCF-7R). This novel codelivery system, which is structurally similar to a kite, is rationally designed to contain multiple functional groups for the targeted delivery and controlled release of the therapeutic cargoes. The self-assembled DNA nanokite achieves efficient gene delivery and exhibits effective inhibition of tumor growth in vitro and in vivo without apparent systemic toxicity. These structurally and chemically well-defined codelivery nanovectors provide a new platform for the development of gene therapeutics for not only cancer but also a wide range of diseases

Genetically Encoded DNA Origami for Gene Therapy In Vivo

DNA origami has played an important role in various biomedical applications, including biosensing, bioimaging, and drug delivery. However, the function of the long DNA scaffold involved in DNA origami has yet to be fully exploited. Herein, we report a general strategy for the construction of a genetically encoded DNA origami by employing two complementary DNA strands of a functional gene as the DNA scaffold for gene therapy. In our design, the complementary sense and antisense strands can be directly folded into two DNA origami monomers by their corresponding staple strands. After hybridization, the assembled genetically encoded DNA origami with precisely organized lipids on the surface can function as the template for lipid growth. The lipid-coated and genetically encoded DNA origami can efficiently penetrate the cell membrane for successful gene expression. After decoration with the tumor-targeting group, the antitumor gene (p53) encoded DNA origami can elicit a pronounced upregulation of the p53 protein in tumor cells to achieve efficient tumor therapy. The targeting group-modified, lipid-coated, and genetically encoded DNA origami has mimicked the functions of cell surface ligands, cell membrane, and nucleus for communication, protection, and gene expression, respectively. This rationally developed combination of folding and coating strategies for genetically encoded DNA origami presents a new avenue for the development of gene therapy

Comparison of three data mining models for prediction of advanced schistosomiasis prognosis in the Hubei province

<div><p>Background</p><p>In order to better assist medical professionals, this study aimed to develop and compare the performance of three models—a multivariate logistic regression (LR) model, an artificial neural network (ANN) model, and a decision tree (DT) model—to predict the prognosis of patients with advanced schistosomiasis residing in the Hubei province.</p><p>Methodology/Principal findings</p><p>Schistosomiasis surveillance data were collected from a previous study based on a Hubei population sample including 4136 advanced schistosomiasis cases. The predictive models use LR, ANN, and DT methods. From each of the three groups, 70% of the cases (2896 cases) were used as training data for the predictive models. The remaining 30% of the cases (1240 cases) were used as validation groups for performance comparisons between the three models. Prediction performance was evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Univariate analysis indicated that 16 risk factors were significantly associated with a patient’s outcome of prognosis. In the training group, the mean AUC was 0.8276 for LR, 0.9267 for ANN, and 0.8229 for DT. In the validation group, the mean AUC was 0.8349 for LR, 0.8318 for ANN, and 0.8148 for DT. The three models yielded similar results in terms of accuracy, sensitivity, and specificity.</p><p>Conclusions/Significance</p><p>Predictive models for advanced schistosomiasis prognosis, respectively using LR, ANN and DT models were proved to be effective approaches based on our dataset. The ANN model outperformed the LR and DT models in terms of AUC.</p></div

Self-Assembled Double-Bundle DNA Tetrahedron for Efficient Antisense Delivery

DNA nanostructures are promising biomaterials capable of arranging multiple functional components with nanometer precision. Here, a double-bundle DNA tetrahedron is rationally designed to integrate with antisense oligonucleotides silencing proto-oncogene <i>c-raf</i> and nuclear targeting peptides. The functionalized DNA tetrahedron can be internalized by A549 cells and assists the delivery of antisense oligonucleotides toward the nucleus to increase the chance to downregulate target mRNA in nucleus and cytoplasm. Antisense strands released from the tetrahedron in response to the intracellular reducing environment can inhibit cell proliferation at a low concentration without transfection reagent. Finally, efficient knockdown of <i>c-raf</i> gene is observed, which verified our design. This designer DNA-based nanocarrier system will open a new avenue for efficient delivery of nucleic acid drugs

The establishment of the DT model for the prognosis of patients with advanced schistosomiasis (C4.5 algorithm).

<p>The establishment of the DT model for the prognosis of patients with advanced schistosomiasis (C4.5 algorithm).</p

ROC curves and AUC values for the advanced schistosomiasis prognosis models constructed with the validation groups using the ANN, DT, and LR models.

<p>The AUC value for the prognosis of patients with advanced schistosomiasis was 0.832 for the ANN model, 0.835 for the LR model, and 0.815 for the DT model. The AUC values of the ANN, DT, and LR models were approximate.</p

ROC curves and AUC values for the advanced schistosomiasis prognosis models constructed with the training groups using the ANN, DT, and LR models.

<p>The AUC value for the prognosis of patients with advanced schistosomiasis was 0.927 for the ANN model, 0.828 for the LR model, and 0.823 for the DT model. The AUC value of the ANN model was superior to those of the DT and LR models.</p

Stimulus-Responsive Plasmonic Chiral Signals of Gold Nanorods Organized on DNA Origami

In response to environmental variations, living cells need to arrange the conformational changes of macromolecules to achieve the specific biofunctions. Inspired by natural molecular machines, artificial macromolecular assemblies with controllable nanostructures and environmentally responsive functions can be designed. By assembling macromolecular nanostructures with noble metal nanoparticles, environmental information could be significantly amplified and modulated. However, manufacturing dynamic plasmonic nanostructures that are efficiently responsive to different stimuli is still a challenging task. Here we demonstrate a stimulus-responsive plasmonic nanosystem based on DNA origami-organized gold nanorods (GNRs). L-shaped GNR dimers were assembled on rhombus-shaped DNA origami templates. The geometry and chiral signals of the GNR nanoarchitectures respond to multiple stimuli, including glutathione reduction, restriction enzyme action, pH change, or photoirradiation. While the glutathione reduction or restriction enzyme caused irreversible changes in the plasmonic circular dichroism (CD) signals, both pH and light irradiation triggered reversible changes in the plasmonic CD. Our system transduces external stimuli into conformational changes and circular dichroism responses in near-infrared (NIR) wavelengths. By this approach, programmable optical reporters for essential biological signals can be fabricated