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The move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium aims to accelerate the development of safer and more-effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium’s plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled—along with validated datasets—into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit—and the knowledge generated by its applications—as a means to accelerate the clinical development of new therapies for a wide range of conditions., This Perspective discusses how the Somatic Cell Genome Editing Consortium aims to accelerate the implementation of safe and effective genome-editing therapies in the clinic.

Delivery technologies for the CRISPR-Cas9 (CRISPR, clustered regularly interspaced short palindromic repeats) gene editing system often require viral vectors, which pose safety concerns for therapeutic genome editing1. Alternatively, cationic liposomal components or polymers can be used to encapsulate multiple CRISPR components into large particles (typically >100 nm diameter); however, such systems are limited by variability in the loading of the cargo. Here, we report the design of customizable synthetic nanoparticles for the delivery of Cas9 nuclease and a single-guide RNA (sgRNA) that enables the controlled stoichiometry of CRISPR components and limits the possible safety concerns in vivo. We describe the synthesis of a thin glutathione (GSH)-cleavable covalently crosslinked polymer coating, called a nanocapsule (NC), around a preassembled ribonucleoprotein (RNP) complex between a Cas9 nuclease and an sgRNA. The NC is synthesized by in situ polymerization, has a hydrodynamic diameter of 25 nm and can be customized via facile surface modification. NCs efficiently generate targeted gene edits in vitro without any apparent cytotoxicity. Furthermore, NCs produce robust gene editing in vivo in murine retinal pigment epithelium (RPE) tissue and skeletal muscle after local administration. This customizable NC nanoplatform efficiently delivers CRISPR RNP complexes for in vitro and in vivo somatic gene editing. Polymer nanocapsules, assembled around a ribonucleoprotein complex of Cas9 nuclease and a single-guide RNA, enable safe and efficient gene editing in vitro and in vivo.

Low-cost flexible microwave circuits with compact size and light weight are highly desirable for flexible wireless communication and other miniaturized microwave systems. However, the prevalent studies on flexible microwave electronics have only focused on individual flexible microwave elements such as transistors, inductors, capacitors, and transmission lines. Thinning down supporting substrate of rigid chip-based monolithic microwave integrated circuits has been the only approach toward flexible microwave integrated circuits. Here, we report a flexible microwave integrated circuit strategy integrating membrane AlGaN/GaN high electron mobility transistor with passive impedance matching networks on cellulose nanofibril paper. The strategy enables a heterogeneously integrated and, to our knowledge, the first flexible microwave amplifier that can output 10 mW power beyond 5 GHz and can also be easily disposed of due to the use of cellulose nanofibril paper as the circuit substrate. The demonstration represents a critical step forward in realizing flexible wireless communication devices., Though flexible microwave integrated circuits (MICs) are desirable for the construction of functional microwave amplifier circuits, realizing low cost III-V-based MMICs remains a challenge. Here, the authors report a heterogeneous integration strategy for the fabrication of flexible low-cost MICs.

This paper presents an analysis of 3-dimensional engineered structural panels (3DESP) made from wood-fiber-based laminated paper composites. Since the existing models for calculating the mechanical behavior of core configurations within sandwich panels are very complex, a new simplified orthogonal model (SOM) using an equivalent element has been developed. This model considers both linear and nonlinear geometrical effects when used to analyze the mechanical properties of 3DESP by transforming repeated elements from a tri-axial ribbed core for bending. Two different conditions were studied in comparison with finite element method (FEM) and I-beam equation. The results showed the SOM was consistent with FEM and the experimental result and were more accurate than the I-beam equation. The SOM considering nonlinear geometric deformation needed more computational effort and was found to match well with a FEM model and had slightly better accuracy compared with the linear SOM. Compared with FEM, the parameters in the linear SOM were easier to modify for predicting point-by-point bending performance. However, while the FEM can provide advanced characteristics of the 3DESP such as strain distribution, the linear SOM provided acceptable deformation accuracy and is proposed for preliminary design with multiple parameters. FEM should be applied for advanced analyses.

Wood pulp cellulose nanofibrils (CNF) thin film is a novel recyclable and biodegradable material. We investigated the microwave dielectric properties of the epoxy coated-CNF thin film for potential broad applications in flexible high speed electronics. The characterizations of dielectric properties were carried out in a frequency range of 1–10 GHz. The dielectric constant and loss tangent were extracted by using measurements of microstrip transmission lines that were built on the epoxy coated-CNF film and combined with Agilent Advanced Design System simulations. The RF property for the epoxy coated-CNF was compared to that of commercial polyethylene terephthalate film (PET). With the comparable microwave properties of non-biodegradable PET film, our study suggests that the epoxy coated-CNF film is a suitable biodegradable and environment-friendly substrate for flexible microwave and other applications.

The simplification of fabrication processes that can define very fine patterns for large-area flexible radio-frequency (RF) applications is very desirable because it is generally very challenging to realize submicron scale patterns on flexible substrates. Conventional nanoscale patterning methods, such as e-beam lithography, cannot be easily applied to such applications. On the other hand, recent advances in nanoimprinting lithography (NIL) may enable the fabrication of large-area nanoelectronics, especially flexible RF electronics with finely defined patterns, thereby significantly broadening RF applications. Here we report a generic strategy for fabricating high-performance flexible Si nanomembrane (NM)-based RF thin-film transistors (TFTs), capable of over 100 GHz operation in theory, with NIL patterned deep-submicron-scale channel lengths. A unique 3-dimensional etched-trench-channel configuration was used to allow for TFT fabrication compatible with flexible substrates. Optimal device parameters were obtained through device simulation to understand the underlying device physics and to enhance device controllability. Experimentally, a record-breaking 38 GHz maximum oscillation frequency fmax value has been successfully demonstrated from TFTs with a 2 μm gate length built with flexible Si NM on plastic substrates.

Supercritical fluid (SCF) N2 was used as a physical foaming agent to fabricate microcellular injection-molded poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV)–poly(butylene adipate-co-terephthalate) (PBAT)–hyperbranched-polymer (HBP)–nanoclay (NC) bionanocomposites. The effects of incorporating HBP and NC on the morphological, mechanical, and thermal properties of both solid and microcellular PHBV–PBAT blends were studied. NC exhibited intercalated structures in solid components, but showed a mixture of exfoliated and intercalated structures in the corresponding microcellular nanocomposites. The addition of NC improved the thermal stability of the resulting nanocomposites. The addition of HBP and NC reduced the cell size and increased the cell density of microcellular components. The addition of HBP and NC enhanced the degree of crystallinity for both solid and microcellular components. Moreover, with the addition of HBP, the area under tan d curve, specific fracture toughness, and strain-at-break of the PHBV-based nanocomposite increased significantly whereas the storage modulus, specific Young’s modulus, and specific tensile strength decreased.

The effects of addition of hyperbranched polyesters (HBPs) and nanoclay on the material properties of both solid and microcellular polylactide (PLA) produced via a conventional and microcellular injection-molding process, respectively, were investigated. The effects of two different types of HBPs (i.e., Boltorn H2004® and Boltorn H20®) at the same loading level (i.e., 12%), and the same type of HBP at different loading levels (i.e., Boltorn H2004® at 6 and 12%), as well as the simultaneous addition of 12% Boltorn H2004® and 2% Cloisite®30B nanoclay (i.e., HBP–nanoclay) on the thermal and mechanical properties (both static and dynamic), and the cell morphology of the microcellular components were noted. The addition of HBPs and/or HBP with nanoclay decreased the average cell size, and increased the cell density. The stress–strain plots of all the solid and microcellular PLA-H2004 blends showed considerable strain softening and cold drawing, indicating a ductile fracture mode. Among the two HBPs, samples with Boltorn H2004® showed higher strain-at-break and specific toughness compared to Boltorn H20®. Moreover, the sample with Boltorn H2004® and nanoclay exhibited the highest strain-at-break (626% for solid and 406% for microcellular) and specific toughness (405% for solid and 334% for microcellular). Finally, the specific toughness, strain-at-break, and specific strength of microcellular samples were found to be lower than their solid counterparts.

Today's consumer electronics, such as cell phones, tablets and other portable electronic devices, are typically made of non-renewable, non-biodegradable, and sometimes potentially toxic (for example, gallium arsenide) materials. These consumer electronics are frequently upgraded or discarded, leading to serious environmental contamination. Thus, electronic systems consisting of renewable and biodegradable materials and minimal amount of potentially toxic materials are desirable. Here we report high-performance flexible microwave and digital electronics that consume the smallest amount of potentially toxic materials on biobased, biodegradable and flexible cellulose nanofibril papers. Furthermore, we demonstrate gallium arsenide microwave devices, the consumer wireless workhorse, in a transferrable thin-film form. Successful fabrication of key electrical components on the flexible cellulose nanofibril paper with comparable performance to their rigid counterparts and clear demonstration of fungal biodegradation of the cellulose-nanofibril-based electronics suggest that it is feasible to fabricate high-performance flexible electronics using ecofriendly materials., The rapid evolution of consumer electronics means that out-of-date devices quickly end up in the scrap heap. Here, the authors fabricate electrical components using biodegradable and flexible cellulose nanofibril paper—a natural sustainable resource derived from wood.

UV-light effects on the polyimide films have been studied by characterizing the film property changes and by measuring the liquid crystal pretilt angle. Infrared, UV-visible and X-ray photoelectron spectroscopy measurements indicate that bond-breaking and oxidation occur during broadband UV-illumination of the film in the air. Free radicals are formed during UV-illumination as evidenced by the analysis of electron spin resonance spectra. Surface tension and polarity are increased after UV-illumination based on the contact angle measurements. While the pretilt angle on the rubbed polyimide film is decreased after nonpolarized UV-illumination, polarized UV-light generates a relatively small pretilt angle on a nonrubbed surface.