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Skin-targeted siRNA therapies require optimized delivery to achieve therapeutic efficacy. Here, authors show that increasing conjugate hydrophobicity enhances siRNA skin retention and gene silencing in porcine and human models while limiting systemic tissue exposure.

Melamine is shown to associate with two poly(thymine) strands, forming antiparallel duplexes that can be used for the dynamic assembly of DNA-based nanostructures.

Nanotubular structures made from different materials are being investigated for applications ranging from sensing to drug delivery, but controlling how they interact with ‘cargo’ molecules has proved challenging. Now, the selective uptake, precise positioning and triggered release of gold nanoparticles has been achieved with nanotubes assembled from triangular DNA building blocks.

Incorporating binding sites for metal ions into DNA strands that assemble into well-defined three-dimensional structures has enabled researchers to build metal-nucleic acid cages. There is potential for the geometry, pore size and chemistry of such materials to be easily tuned, which may prove useful for applications in molecular sensing and encapsulation.

DNA nanotubes are attractive building blocks for the assembly of complex arrays. An efficient solid-state synthesis for producing surface-grafted, robust nanotubes has now been devised. Rungs are incorporated in a stepwise manner so that each one is addressable. Using fluorescent tags, the nanotube growth was visualized at the single-molecule level.

Nature uses out-of-equilibrium systems to control hierarchical assembly. Now, a dissipative chemical system has been shown to slowly release monomer DNA strands from a high-energy reservoir, regulating self-assembly by switching the mechanism of supramolecular polymerization at the single-molecule level. This process heals fibre defects, converting branched, heterogeneous networks into nanocable superstructures.

Wu and colleagues show that T_H17 cells arising in the gut in response to segmented filamentous bacteria can convert to highly mobile follicular helper T_FH17 cells, emigrate to the spleen and regulate auto-antibody production and arthritis severity.

The combination of dynamic, energy driven folding and growth with structural stiffness and length control is difficult to achieve in synthetic polymer self-assembly. Here the authors show that highly charged, monodisperse DNA oligomers assemble via seeded growth into length-controlled supramolecular fibers during heating.

Assembling defined sequences of DNA is important for many applications, but the synthesis becomes more difficult as the target size increases. Here, the authors report a method for assembling DNA by combining smaller strands, with the final structure determined by the order of addition of the fragments.

The site-specific incorporation of dendritic DNA amphiphiles into a DNA cage controls whether the resultant structures show intermolecular self-assembly or intramolecular assembly. Intramolecular assembly creates a hydrophobic core within the cage that is capable of encapsulating small molecules. These molecules can be released on addition of specific DNA strands.

DNA nanotubes can potentially act as stiff interconnects, tracks for molecular motors and nanoscale drug carriers. Researchers have now reported a modular approach to DNA nanotube synthesis that can create geometrically well-defined triangular and square tubes. The method allows parameters such as geometry, stiffness and single- or double-stranded character to be tuned, and could provide access to designer nanotubes for a range of applications.

Here the authors provide results from a genomic epidemiology study of a cholera outbreak in Lebanon, showing that it was caused by two Vibrio cholerae strains of serogroup O1 (El Tor biotype), namely an AFR15 sublineage related to South Asian isolates and extensively drug-resistant Yemeni AFR13.

Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Here, Park et al. identify LETMD1 as a mitochondrial matrix protein enriched in brown adipose tissue (BAT) and reveal a crucial role for it in maintaining brown adipocyte mitochondrial OXPHOS and thermogenesis upon cold stimulus.

The field of DNA nanotechnology takes the DNA molecule out of its biological context and uses its information to assemble structural motifs and connect these motifs together. In this Review, a historical account of the field and the approaches used to assemble DNA nanostructures are outlined, followed by a discussion of emerging applications.

Benegiamo et al. identify genetic variants of the mitochondrial supercomplex assembly factor COX7A2L in the skeletal muscle of mice and humans that promote cardiorespiratory fitness.

DNA nanostructures are typically used as molecular scaffolds. Now, it has been shown that they can also act as reusable templates for ‘molecular printing’ of DNA strands onto gold nanoparticles. The products inherit the recognition elements of the parent template: number, orientation and sequence asymmetry of DNA strands. This converts isotropic nanoparticles into complex building blocks.

The genetic basis of atopic dermatitis is not fully understood. Here, the authors find 91 genetic loci associated with atopic dermatitis in a GWAS of >1million individuals, which highlight the importance of systemic immune regulation.

Cyanuric acid, a small molecule with three thymine-like faces, reprogrammes the assembly of unmodified poly(adenine) into long fibres with a unique internal structure. The association of adenine and cyanuric acid units into a hexameric rosette motif brings together poly(adenine) triplexes with subsequent cooperative polymerization.

Mechanobiological signals have been reported to contribute to abdominal aortic aneurysm (AAA) development. Here the authors report that the microskeletal stiffness and a Piezo1-mediated mechanism influence vascular smooth muscle cell mechanosensation and AAA disease development.

DNA–polymer conjugates are attractive materials that combine the programmability of nucleic acid assembly with polymer functionality. Now, through a DNA cube template, monodisperse polymer particles have been imprinted with several DNA strands in pre-designed orientations— each independently set and addressable. The resulting hybrid particles can further assemble into well-defined, non-centrosymmetric structures.

Testing the association between genetic variants and a range of phenotypes can assist drug development. Here, in a phenome-wide association study in up to 697,815 individuals, Diogo et al. identify genotype–phenotype associations predicting efficacy, alternative indications or adverse drug effects.

Roy et al. quantify the impact of a high-fat diet across genetically diverse strains of mice, revealing a generally negative effect on lifespan but also a wide variability.

Genetic studies of eczema to date have mostly explored common genetic variation. Here, the authors perform a large meta-analysis for common and rare variants and discover 8 loci associated with eczema. Over 20% of the heritability of the condition is attributable to rare variants.

Human disease genetics is extended to the identification of individuals who remain healthy despite carrying highly penetrant disease-causing mutations.

Hakon Hakonarson and colleagues report the identification of two new susceptibility loci for inflammatory bowel disease (IBD). One variant is near a gene encoding tumor necrosis factor receptor subfamily member 6B and is associated with increased levels of this protein in serum from individuals with IBD.

Identification of gene expression changes between healthy and diseased individuals can reveal mechanistic insights and biomarkers. Here, the authors propose a bi-directional transcriptome-wide Mendelian Randomization approach to assess causal effects between gene expression and complex traits.

Anneke den Hollander, Patsy Nishina and colleagues report heterozygous missense mutations in CTNNA1 in three families with butterfly-shaped pigment dystrophy. Ctnna1-mutant mice display a similar phenotype and show increased cell shedding and large multinucleated cells in the retinal pigment epithelium, suggesting defects in intercellular adhesion and cytokinesis.

Hakon Hakonarson and colleagues identify variants near TSLP at 5q22 associated with pediatric eosinophilic esophagitis. They further show that TSLP is overexpressed in esophageal biopsies of cases compared to controls and that the risk variants are associated with elevated TSLP expression.

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impairments in social and communication skills. Accumulating evidence suggests a genetic component to ASDs, and here a two-stage, genome-wide approach is used to identify candidate genomic loci enriched in ASD cases. The majority of these loci are found to be involved in neuronal adhesion and ubiquitin degradation, suggesting novel susceptibility mechanisms.

HCCAA is a dominantly inherited disease which causes brain hemorrhages as a result of mutant cystatin C aggregation in carriers. Here, the authors show that n- acetyl cysteine can prevent aggregation of mutant protein in a cell model system and reverse protein deposition in the skin of mutation-carrying subjects.

The development of asthma following eczema is known as the atopic march. Here the authors conduct a GWAS on affected children and identify two novel loci associated with the disease phenotype.

An analytical framework based on transcriptome-wide association and electronic medical records provides insights into the relationship between plasma lipids and complex diseases on a phenome-wide scale.

Although structural variation has been previously associated with autism spectrum disorders, this study reports a genome-wide significant association of common variants with susceptibility to this disorder group. The results implicate neuronal cell-adhesion molecules in the pathogenesis of this group of neurodevelopmental and neuropsychiatric disorders.

Complex assembly pathways often involve transient, partly-formed intermediates that are challenging to characterize. Here, the authors present a simple and rapid spectroscopic thermal hysteresis method for mapping the energy landscapes of supramolecular assembly.

Autoimmune diseases are genetically complex disorders that affect up to 10% of the Western population. Here Li et al. quantify the heritability of a range of autoimmune diseases in the largest paediatric cohort examined to date, illustrating that genetic and non-genetic components variably contribute to the susceptibility of each disease.

A meta-analysis across ten pediatric autoimmune diseases reveals shared genetic architecture and novel susceptibility loci.

Chromosomal abnormalities such as 11q deletion are associated with poor prognosis in neuroblastoma. Here, the authors perform a genome-wide association study and identify an association between a variant within a Matrix metalloproteinase (MMP) gene member, MMP20, and 11q-deletion subtype neuroblastoma.

Associations of copy number variations (CNVs) with complex traits are challenging to study because of their low frequency. Here, the authors analyse SNP array and array comparative genomic hybridization data of 100,028 individuals and report their associations with immune-related, cardiometabolic and neuropsychiatric diseases as well as cancer.

Lavinia Paternoster and colleagues report a meta-analysis of genome-wide association studies of atopic dermatitis. They report three newly identified associated loci near OVOL1 and ACTL9 and in KIF3A.

Klaus Bønnelykke and colleagues identify a common variant in CDHR3 associated with early childhood asthma with severe exacerbations. CDHR3 encodes a cell adhesion protein expressed at high levels in airway epithelium, suggesting a role for altered epithelial integrity in asthma pathogenesis.

Vivianna Van Deerlin and colleagues report that common variants at 7p21 are associated with a subtype of frontotemporal lobar degeneration marked by TDP-43 inclusions. They further show that the risk alleles are associated with elevated brain expression of TMEM106B, which resides at the peak of association on 7p21.

Parkin, an ubiquitin ligase whose mutations are associated with early development of Parkinson's disease, possesses a RING domain, suggesting it can modulate transcription. Parkin represses the expression of p53 both in fibroblasts and mice brains, independently of its ligase activity, and patient brain samples exhibit high levels of p53.

A recurrent gain-of-function mutation in ARAF causes lymphatic anomaly in two unrelated patients, and treating one of the patients with an FDA-approved MEK inhibitor resulted in a remarkable recovery, exemplifying the power of precision medicine.

Hakon Hakonarson and colleagues report a genome-wide copy number variation study in 3,506 cases of attention-deficit hyperactivity disorder. The authors identify a statistically significant enrichment of CNVs impacting metabotropic glutamate receptor genes.

Hakon Hakonarson and colleagues report the discovery of five new regions associated with susceptibility to early-onset inflammatory bowel disease. They also identify multiple loci previously implicated in the etiology of adult-onset Crohn's disease and/or ulcerative colitis as risk factors for early-onset forms of these diseases.