A general genome editing strategy using CRISPR lipid nanoparticle spherical nucleic acids.

Genome editing with CRISPR-Cas systems hold promise for treating a wide range of genetic disorders and cancers. However, efficient delivery of genome editors remains challenging due to the requirement for the simultaneous delivery or intracellular generation of Cas proteins, guide RNAs, and, in some applications, donor DNAs. Furthermore, the immunogenicity and toxicity of delivery vehicles can limit the safety and efficacy of genetic medicines.

33 Unresolved Questions in Nanoscience and Nanotechnology.

Significant advances in science and engineering often emerge at the intersections of disciplines. Nanoscience and nanotechnology are inherently interdisciplinary, uniting researchers from chemistry, physics, biology, medicine, materials science, and engineering. This convergence has fostered novel ways of thinking and enabled the development of materials, tools, and technologies that have transformed both basic and applied research, as well as how we address critical societal challenges.

Accelerating the Pace of Oxygen Evolution Reaction Catalyst Discovery through Megalibraries.

Iridium (Ir) catalysts are essential for the acidic oxygen evolution reaction (OER) in proton-exchange membrane water electrolyzers (PEMWEs), but their high cost, scarcity, and geographical concentration limit large-scale adoption. In addition, the discovery of non-Ir alternatives is slow due to the vast design space possible. Here, a "megalibrary" is used to explore the catalytic activity of ∼156 million distinct nanostructures comprised of Ru, Co, Mn, and Cr to find alternatives to Ir catalysts for OER.

Programming Defects and Cavities into Colloidal Crystals Engineered With DNA.

Taking inspiration from seed-mediated crystal growth in atomic and molecular systems, a strategy is developed for incorporating particle and volume defects into the interior of colloidal crystals consisting of programmable atom equivalents (PAEs, oligonucleotide-functionalized nanoparticles) assembled with DNA. Discrete PAEs spanning a range of shapes, sizes, and compositions serve as nucleation sites for seed-mediated colloidal crystal growth and are incorporated into the centers of colloidal crystal lattices as cavities. Importantly, seed PAE shapes or sizes that are geometrically mismatched with the colloidal crystal lattice symmetry introduce defects such as local lattice disorder and long-range grain boundaries that arise through geometric frustration.

The emerging era of structural nanomedicine.

The lack of structural definition in nanomedicines limits therapeutic efficacy and complicates regulatory approval. Here, we emphasize that defining, designing and optimizing the structures of nanomedicine are critical to developing effective therapies because their architectures - not just the identity of their components - determines potency.

Automated image segmentation for accelerated nanoparticle characterization.

Recent developments in materials science have made it possible to synthesize millions of individual nanoparticles on a chip. However, many steps in the characterization process still require extensive human input. To address this challenge, we present an automated image processing pipeline that optimizes high-throughput nanoparticle characterization using intelligent image segmentation and coordinate generation.

Blueprints for Better Drugs: The Structural Revolution in Nanomedicine.

Structural nanomedicines are engineered constructs that arrange therapeutic components into well-defined architectures to maximize efficacy. Their multivalent, multifunctional design offers key advantages over unstructured formulations, including targeted delivery, expanded therapeutic windows, and enhanced target engagement. The mRNA COVID-19 vaccines exemplify their transformative potential.

Leveraging Protein-Ligand and DNA Interactions to Control Hydrogel Mechanics.

Biomacromolecules can serve as molecularly precise building blocks for hydrogel materials, dictating material properties that depend on the chemical identity and interactions of the individual components. Herein, we introduce biomolecular hydrogels where ligand-functionalized DNA sequences form the hydrogel backbone and multivalent protein-ligand interactions form supramolecular cross-links. In these hydrogels, we can independently leverage the programmable rigidity of DNA (i.

Biomineralization of semiconductor quantum dots using DNA-functionalized protein nanoreactors.

Proteins can template the heterogeneous nucleation and growth of size-confined nanocrystals. However, protein-templated mineralization often leads to particles that exhibit low colloidal stability, poor crystal quality, and/or diminished photoluminescence. Here, we report protein cage-spherical nucleic acids (SNAs) that can be used as nanoreactors for quantum dot (QD) synthesis and subsequent intracellular delivery.

Cocrystals combining order and correlated disorder via colloidal crystal engineering with DNA.

Colloidal cocrystallization enables the formation of multicomponent materials with unique physicochemical properties, yet the role of nanoparticle (NP) shape and specific ligand interactions to cocrystallize anisotropic and isotropic NPs, with order and correlated disorder, remains underexplored. Here, geometry-inspired strategies along with programmable DNA interactions are combined to achieve structural control of colloidal cocrystal assemblies. Coassembling polyhedral and spherical NPs with complementary DNA yields two classes of cocrystals: one where both components order, and another where polyhedral NPs form a periodic lattice, while spherical NPs remain disordered but spatially correlated with polyhedral edges and corners.

Nanofabrication for Nanophotonics.

Nanofabrication, a pivotal technology at the intersection of nanoscale engineering and high-resolution patterning, has substantially advanced over recent decades. This technology enables the creation of nanopatterns on substrates crucial for developing nanophotonic devices and other applications in diverse fields including electronics and biosciences. Here, this mega-review comprehensively explores various facets of nanofabrication focusing on its application in nanophotonics.

Traversing the Periodic Table through Phase-Separating Nanoreactors.

Phase-separating nanoreactors, generated through either Dip Pen Nanolithography (DPN) or Polymer Pen Lithography (PPL) and capable of single nanoparticle formation, are compatible with almost every relevant element from the periodic table. This advance overcomes one of the most daunting limitations in high throughput materials discovery, specifically enabling the synthesis of broad swaths of the materials genome. Indeed, the platform is compatible with at least 52 metal elements of interest and almost an infinite number of combinations.

Radiation Chemistry in Environmental Transmission Electron Microscopy.

Environmental transmission electron microscopy (E-TEM) enables direct observation of nanoscale chemical processes crucial for catalysis and materials design. However, the high-energy electron probe can dramatically alter reaction pathways through radiolysis, the dissociation of molecules under electron beam irradiation. While extensively studied in liquid-cell TEM, the impact of radiolysis in gas phase reactions remains unexplored.

Organic Modulators Enable Morphological Diversity in Colloidal Crystals Engineered with DNA.

Colloidal crystal engineering with DNA is a powerful way of generating a wide variety of crystals spanning over 90 different symmetries. However, in many cases, crystals with well-defined habits are difficult, if not impossible, to make, in part due to rapid crystal defect formation and propagation. This is especially true in the case of face-centered cubic (FCC) structures.

Creating chromaticity palettes and identifying white light emitters through nanocrystal megalibraries.

Halide perovskites are used to fabricate energy-efficient optoelectronic devices. Determining which compositions yield desired chromatic responses is challenging, especially when doping strategies are used. Here, we report a way of mapping the compositional space of halide perovskites to generate a light emission or "chromaticity" palette.

DNA Dendron Tagging as a Universal Way to Deliver Proteins to Cells.

The use of proteins as intracellular probes and therapeutic tools is often limited by poor intracellular delivery. One approach to enabling intracellular protein delivery is to transform proteins into spherical nucleic acid (proSNA) nanoconstructs, with surfaces chemically modified with a dense shell of radially oriented DNA that can engage with cell-surface receptors that facilitate endocytosis. However, proteins often have a limited number of available reactive surface residues for DNA conjugation such that the extent of DNA loading and cellular uptake is restricted.

Manipulating metal-ligand binding in allosteric coordination complexes through ring strain.

The weak-link approach (WLA) to organometallic complexes offers a powerful method to create allosteric shape-shifting coordination complexes. However, chemically tuning the metal-ligand interactions entails challenging syntheses. This study explores the influence of ring strain on the lability of the platinum-sulfur interaction within WLA complexes, providing a simpler alternative to chemical modifications.

Nomadic Nanomedicines: Medicines Enabled by the Paracrine Transfer Effect.

In nanomedicine, the cellular export of nanomaterials has been less explored than uptake. Traditionally viewed in a negative light, recent findings highlight the potential of nanomedicine export to enhance therapeutic effects. This Perspective examines key pathways for export and how nanomaterial design affects removal rates.

Early Folding Dynamics of i-Motif DNA Revealed by pH-Jump Time-Resolved X-ray Solution Scattering.

The i-motif is a pH-responsive cytosine-rich oligonucleotide sequence that forms, under acidic conditions, a quadruplex structure. This tunable structural switching has made the i-motif a useful platform for designing pH-responsive nanomaterials. Despite the widespread application of i-motif DNA constructs as biomolecular switches, the mechanism of i-motif folding on the atomic scale has yet to be established.

DNA-Regulated Multi-Protein Complement Control.

In nature, the interactions between proteins and their complements/substrates can dictate complex functions. Herein, we explore how DNA on nucleic acid modified proteins can be used as scaffolds to deliberately control interactions with a peptide complement (by adjusting length, sequence, and rigidity). As model systems, split GFPs were covalently connected through DNA scaffolds (36-58 bp).

Microcrystal Growth Pathways Investigated with Machine Learning Segmentation and Classification in Scanning Electron Microscopy.

Advances in electron microscopy have revolutionized material characterization on the nano- and microscales, providing important insights into local ordering, structure, and size and quality distributions. While shape and size can be rigorously quantified through microscopy, it is often limited to local structure analysis and fails to describe bulk sample quality. Herein, a flexible machine learning (ML) tool is described that can segment and classify faceted crystals in scanning electron microscopy (SEM) micrographs to determine sample quality through the crystal size and product distribution.

Implantable Fluorogenic DNA Biosensor for Stress Detection.

Implantable sensors that can monitor analytes related to cognitive and physiological status have gained significant focus in recent years. We have developed an implantable biosensor to detect dehydroepiandrosterone sulfate (DHEA-S), a biomarker related to stress. The biosensor strategy was based on the principle of forced intercalation (FIT) aptamers designed to detect subtle intramolecular changes during aptamer-target binding events.

High Temperature, Isothermal Growth Promotes Close Packing and Thermal Stability in DNA-Engineered Colloidal Crystals.

We report a strategy to accelerate the synthesis and increase the crystallinity of colloidal crystals (CCs) engineered with DNA. Specifically, by holding the DNA-modified Au particle building blocks above the of the DNA bonding elements (i.e.

Engineering Anisotropy into Organized Nanoscale Matter.

Programming the organization of discrete building blocks into periodic and quasi-periodic arrays is challenging. Methods for organizing materials are particularly important at the nanoscale, where the time required for organization processes is practically manageable in experiments, and the resulting structures are of interest for applications spanning catalysis, optics, and plasmonics. While the assembly of isotropic nanoscale objects has been extensively studied and described by empirical design rules, recent synthetic advances have allowed anisotropy to be programmed into macroscopic assemblies made from nanoscale building blocks, opening new opportunities to engineer periodic materials and even quasicrystals with unnatural properties.