RPE-Directed Gene Therapy Improves Mitochondrial Function in Murine Dry AMD Models.

Age-related macular degeneration (AMD) is the most common cause of blindness in the aged population. However, to date there is no effective treatment for the dry form of the disease, representing 85-90% of cases. AMD is an immensely complex disease which affects, amongst others, both retinal pigment epithelium (RPE) and photoreceptor cells and leads to the progressive loss of central vision. Mitochondrial dysfunction in both RPE and photoreceptor cells is emerging as a key player in the disease. There are indications that during disease progression, the RPE is first impaired and RPE dysfunction in turn leads to subsequent photoreceptor cell degeneration; however, the exact sequence of events has not as yet been fully determined. We recently showed that AAV delivery of an optimised NADH-ubiquinone oxidoreductase (NDI1) gene, a nuclear-encoded complex 1 equivalent from S. cerevisiae, expressed from a general promoter, provided robust benefit in a variety of murine and cellular models of dry AMD; this was the first study employing a gene therapy to directly boost mitochondrial function, providing functional benefit in vivo. However, use of a restricted RPE-specific promoter to drive expression of the gene therapy enables exploration of the optimal target retinal cell type for dry AMD therapies. Furthermore, such restricted transgene expression could reduce potential off-target effects, possibly improving the safety profile of the therapy. Therefore, in the current study, we interrogate whether expression of the gene therapy from the RPE-specific promoter, Vitelliform macular dystrophy 2 (VMD2), might be sufficient to rescue dry AMD models.

Dipolar-Coupled Entangled Molecular 4f Qubits.

We demonstrate by use of continuous wave- and pulse-electron paramagnetic resonance spectroscopy on oriented single crystals of magnetically dilute YbIII ions in Yb0.01Lu0.99(trensal) that molecular entangled two-qubit systems can be constructed by exploiting dipolar interactions between neighboring YbIII centers. Furthermore, we show that the phase memory time and Rabi frequencies of these dipolar-interaction-coupled entangled two-qubit systems are comparable to the ones of the corresponding single qubits.

Plasmon-Assisted Ammonia Electrosynthesis.

Ammonia is a promising liquid-phase carrier for the storage, transport, and deployment of carbon-free energy. However, the realization of an ammonia economy is predicated on the availability of green methods for the production of ammonia powered by electricity from renewable sources or by solar energy. Here, we demonstrate the synthesis of ammonium from nitrate powered by a synergistic combination of electricity and light. We use an electrocatalyst composed of gold nanoparticles, which have dual attributes of electrochemical nitrate reduction activity and visible-light-harvesting ability due to their localized surface plasmon resonances. Plasmonic excitation of the electrocatalyst induces ammonium synthesis with up to a 15× boost in activity relative to conventional electrocatalysis. We devise a strategy to account for the effect of photothermal heating of the electrode surface, which allows the observed enhancement to be attributed to non-thermal effects such as energetic carriers and charged interfaces induced by plasmonic excitation. The synergy between electrochemical activation and plasmonic activation is the most optimal at a potential close to the onset of nitrate reduction. Plasmon-assisted electrochemistry presents an opportunity for conventional limits of electrocatalytic conversion to be surpassed due to non-equilibrium conditions generated by plasmonic excitation.

Enhanced Functional Properties of Three DNA Origami Nanostructures as Doxorubicin Carriers to Breast Cancer Cells.

Previous studies have shown that chemotherapeutic efficacy could be enhanced with targeted drug delivery. Various DNA origami nanostructures have been investigated as drug carriers. Here, we compared drug delivery functionalities of three similar DNA origami nanostructures, Disc, Donut, and Sphere, that differ in structural dimension. Our results demonstrated that Donut was the most stable and exhibited the highest Dox-loading capacity. MUC1 aptamer modification in our nanostructures increased cellular uptake in MUC1-high MCF-7. Among the three nanostructures, unmodified Donut exerted the highest Dox cytotoxicity in MCF-7, and MUC1 aptamer modification did not further improve its effect, implicating that Dox delivery by Donut was efficient. However, all Dox-loaded nanostructures showed comparable cytotoxicity in MDA-MB-231 due to the innate sensitivity of this cell line to Dox. Our results successfully demonstrated that functional properties of DNA origami nanocarriers could be tuned by structural design, and three-dimensional Donut appeared to be the most efficient nanocarrier.

The applications of functionalized DNA nanostructures in bioimaging and cancer therapy.

Deoxyribonucleic acid (DNA) is a molecular carrier of genetic information that can be fabricated into functional nanomaterials in biochemistry and engineering fields. Those DNA nanostructures, synthesized via Watson-Crick base pairing, show a wide range of attributes along with excellent applicability, precise programmability, and extremely low cytotoxicity in vitro and in vivo. In this review, the applications of functionalized DNA nanostructures in bioimaging and tumor therapy are summarized. We focused on approaches involving DNA origami nanostructures due to their widespread use in previous and current reports. Non-DNA origami nanostructures such as DNA tetrahedrons are also covered. Finally, the remaining challenges and perspectives regarding DNA nanostructures in the biomedical arena are discussed.

Area-Selective Atomic Layer Deposition of Metal Oxides on DNA Nanostructures and Its Applications.

We demonstrate area-selective atomic layer deposition (ALD) of oxides on DNA nanostructures. Area-selective ALD of Al2O3, TiO2, and HfO2 was successfully achieved on both 2D and 3D DNA nanostructures deposited on a polystyrene (PS) substrate. The resulting DNA-inorganic hybrid structure was used as a hard mask to achieve deep etching of a Si wafer for antireflection applications. ALD is a widely used process in coating and thin film deposition; our work points to a way to pattern oxide materials using DNA templates and to enhance the chemical/physical stability of DNA nanostructures for applications in surface engineering.

Exploring the Addressability of DNA Decorated Multifunctional Gold Nanoparticles with DNA Origami Template.

The hybridization of gold nanoparticles (AuNPs), along with other nanomaterials, has encouraged applications in biomedical imaging, plasmonic enhancement, and catalysts. However, the rational organization of AuNPs in nanotechnology fields remains difficult, which might require multiaddressability of nanoparticles for heterogeneous conjugation. In this work, multifunctional AuNPs were developed by conjugation of two types of DNA strands containing different sequences, which allowed the AuNPs to recognize multiple binding sites. The ratio of different sequences of DNA, and the different lengths of coding DNA oligos on the surface of the AuNPs, had varied influences on the functionality of the multifunctional DNA-AuNPs. This new type of DNA-decorated nanoparticles will enhance the diversity and complexity of nanoparticle-based bottom-up fabrication in materials science and bionanotechnology.

Metal-ion responsive reversible assembly of DNA origami dimers: G-quadruplex induced intermolecular interaction.

We present a novel metal-ion stimulated organization of DNA origami nanostructures by employing G-quadruplexes as stimuli-responsive bridges. The reversible assembly process of DNA origami was the result of conformational changes between the G-quadruplex and its single-strand state induced by monovalent cations. This study might stimulate a new design of responsive DNA-based intelligent nanomaterials.