Article
|
Open Access
Featured
-
-
Article
| Open AccessDesign of a platform technology for systemic delivery of siRNA to tumours using rolling circle transcription
RNA interference has provided a promising tool to suppress the expression of specific genes associated with human diseases. Here, the authors present a platform technology for the systemic delivery of siRNA to tumour sites using rolling circle transcription.
- Mihue Jang
- , Jong Hwan Kim
- & Hyung Jun Ahn
-
Article
| Open AccessGram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications
Coordination polymers are promising drug delivery nanomaterials as their structural properties can be easily controlled. Here, Wang et al. prepare coordination nanodots that integrate cancer imaging and therapeutic functions with beneficial renal clearance.
- Fuyao Liu
- , Xiuxia He
- & Zhenxin Wang
-
Article |
A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models
The encapsulation of a drug into nanoparticles can be a useful way control and improve its efficacy. Here, the authors conjugate paclitaxel to recombinant chimeric polypeptides that self-assemble into therapeutic nanoparticles that outperform Abraxane in murine tumour models.
- Jayanta Bhattacharyya
- , Joseph J. Bellucci
- & Ashutosh Chilkoti
-
Article
| Open AccessA potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus
Monoclonal antibodies with broadly neutralizing activity are being developed as potential treatment of influenza infections. Here, the authors describe a broadly neutralizing antibody with an unusual mode of binding to viral haemagglutinin, which has been isolated from patients convalescent from pandemic H1N1 influenza infection.
- Ying Wu
- , MyungSam Cho
- & Ruben O. Donis
-
Article
| Open AccessThe development and characterization of synthetic minimal yeast promoters
Endogenous fungal gene promoters can be hundreds of base pairs long, limiting their use in synthetic biology and biotechnology. Here Redden and Alper screen a library of synthetic promoter elements to generate compact DNA sequences of ∼100 base pairs able to drive high levels of gene expression.
- Heidi Redden
- & Hal S. Alper
-
Article
| Open AccessSelf-organizing human cardiac microchambers mediated by geometric confinement
Organogenesis is orchestrated by biochemical and biophysical stimuli. Here, Ma et al. generate a micro-patterned surface that provides mechanical cues which, when combined with biochemical signals, drive human pluripotent stem cells’ differentiation into beating cardiac microchambers resembling primitive hearts.
- Zhen Ma
- , Jason Wang
- & Kevin E. Healy
-
Article
| Open AccessA highly selective biosynthetic pathway to non-natural C50 carotenoids assembled from moderately selective enzymes
Synthetic engineering of complex pathways is often hindered by pathway branching and generation of non-target compounds. Here, the authors show that by judicious combination of moderately selective enzyme variants, a non-natural C50 carotenoid can be generated in bacteria with minimal production of unwanted compounds.
- Maiko Furubayashi
- , Mayu Ikezumi
- & Daisuke Umeno
-
Article |
A drug-specific nanocarrier design for efficient anticancer therapy
Telodendrimers are versatile and robust nanoparticle-based drug carriers. From a screen of potential small-molecule building blocks, Shi et al.identify rhein-containing telodendrimers as stable and effective nanocarriers of doxorubicin for treating a xenograft Raji lymphoma model.
- Changying Shi
- , Dandan Guo
- & Juntao Luo
-
Review Article |
The role of mechanics in biological and bio-inspired systems
There are many examples in nature of biological materials having developed interesting mechanical properties to enhance their functional performance. Here, Egan et al. review these materials and how they can inspire the design of biomimetic mechanical systems.
- Paul Egan
- , Robert Sinko
- & Sinan Keten
-
Article
| Open AccessTwo-dimensional isobutyl acetate production pathways to improve carbon yield
Achieving high carbon yields is crucial for biotechnological production of metabolites in engineered microorganisms. Here, Tashiroet al. generate E. colistrains that produce acetyl-CoA and a derived metabolite (isobutyl acetate) in the absence of pyruvate decarboxylation, leading to increased carbon yields.
- Yohei Tashiro
- , Shuchi H. Desai
- & Shota Atsumi
-
Article
| Open AccessForce-induced chemical reactions on the metal centre in a single metalloprotein molecule
The investigation of the chemical reactivity of metal centres in metalloproteins in aqueous solution is challenging. Here, the authors demonstrate the use of single molecule force spectroscopy to study the chemical reactivity of the iron-sulfur centre in rubredoxin in aqueous solution.
- Peng Zheng
- , Guilherme M. Arantes
- & Hongbin Li
-
Article |
A primase subunit essential for efficient primer synthesis by an archaeal eukaryotic-type primase
Archaea encode an eukaryotic-type primase comprising a catalytic subunit PriS and a noncatalytic subunit PriL. Here, the authors identify in an archaeon Sulfolobus solfataricus an essential noncatalytic subunit of primase, PriX, that forms PriSLX trimer and increases the efficiency of primer synthesis.
- Bing Liu
- , Songying Ouyang
- & Li Huang
-
Article
| Open AccessArtificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue
Avoiding central cell necrosis at the centre of large engineered tissue constructs is an important issue forin vitrotissue engineering. Here, the authors demonstrate that this problem may be overcome by oxygenating human mesenchymal stem cells with artificial membrane-binding proteins.
- James P. K. Armstrong
- , Rameen Shakur
- & Anthony P. Hollander
-
Article
| Open AccessDevelopment and rescue of human familial hypercholesterolaemia in a xenograft mouse model
Familial hypercholesterolemia (FH) is a congenital disease associated with high plasma cholesterol levels. Here, the authors recapitulate FH in chimeric mice, in which livers are repopulated with hepatocytes from an FH patient, and successfully correct the disease using adenovirus-mediated gene therapy.
- Beatrice Bissig-Choisat
- , Lili Wang
- & Karl-Dimiter Bissig
-
Article
| Open AccessSingle molecule-level detection and long read-based phasing of epigenetic variations in bacterial methylomes
Bacterial DNA methylation is involved in many processes, from host defense to antibiotic resistance, however current methods for examining methylated genomes lack single-cell resolution. Here Beaulaurier et al. present Single Molecule Modification Analysis of Long Reads, a new tool for de novodetection of epigenetic heterogeneity.
- John Beaulaurier
- , Xue-Song Zhang
- & Gang Fang
-
Article
| Open AccessProximity-dependent initiation of hybridization chain reaction
Proximity ligation assays are a sensitive method for detecting protein interactions, but require the addition of enzymes. Here the authors introduce proxHCR, an enzyme-free method of detecting interactions in close proximity by inducing a hybribization chain reaction (HCR) of fluorescently labelled oligonucleotides.
- Björn Koos
- , Gaëlle Cane
- & Ola Söderberg
-
Article
| Open AccessPhasing of single DNA molecules by massively parallel barcoding
DNA phasing information — the determination of which specific sequences belong to the same DNA molecule—is not easily obtained from sequencing applications that rely on short reads. Here the authors develop a phasing method based on massively parallel barcoding of single DNA molecules.
- Erik Borgström
- , David Redin
- & Afshin Ahmadian
-
Article
| Open AccessPharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis
Adverse drug reactions are an important clinical problem. Here the authors combine information about drug-induced gene expression changes and genetic variability of patients with a genome-scale metabolic model to identify drug-induced changes in cellular metabolism that may be linked to drug side effects.
- Daniel C. Zielinski
- , Fabian V. Filipp
- & Bernhard O. Palsson
-
Article
| Open AccessTargeted DNA degradation using a CRISPR device stably carried in the host genome
The ability to contain and destroy synthetically engineered microorganisms is an important consideration with environmental, industrial and intellectual property implications. Here Caliando et al. design and demonstrate a stably integrated CRISPR-based system for targeted DNA destruction.
- Brian J. Caliando
- & Christopher A. Voigt
-
Article
| Open AccessAtomistic design of microbial opsin-based blue-shifted optogenetics tools
Retinal-bound opsins are widely used tools for optical control of neuronal activity in vivo, so called optogenetics. Here, using molecular simulations, biochemistry, electrophysiology and X-ray crystallography, the authors present new molecular design principles for the generation of blue-shifted variants of microbial rhodopsins.
- Hideaki E. Kato
- , Motoshi Kamiya
- & Osamu Nureki
-
Article
| Open AccessGreen fluorescent protein nanopolygons as monodisperse supramolecular assemblies of functional proteins with defined valency
Supramolecular protein assemblies can provide novel nano-architectures with diverse structures and functions. Here, the authors report a fabrication strategy for a series of monodisperse protein oligomers, which allows valency-controlled display of various functional proteins.
- Young Eun Kim
- , Yu-na Kim
- & Yongwon Jung
-
Article
| Open AccessExpression of heterologous sigma factors enables functional screening of metagenomic and heterologous genomic libraries
Screening genomic or metagenomic libraries for interesting products or activities is often hampered by poor gene expression in a heterologous host. Here the authors show that the expression of a Lactobacillus sigma factor greatly enhances transcription of heterologous and environmental DNA in E. coli.
- Stefan M. Gaida
- , Nicholas R. Sandoval
- & Eleftherios T. Papoutsakis
-
Article |
Reinforcement of hydrogels using three-dimensionally printed microfibres
Hydrogels are commonly used materials for tissue engineering, but they can lack the structural properties required for load-bearing and mechanical applications. Here, the authors prepare a polycaprolactone scaffold using melt-electrospinning to reinforce a gelatin methacrylamide hydrogel.
- Jetze Visser
- , Ferry P.W. Melchels
- & Jos Malda
-
Article |
In vivo model with targeted cAMP biosensor reveals changes in receptor–microdomain communication in cardiac disease
cAMP is a second messenger that acts in distinct intracellular locations regulating diverse cellular functions. Here the authors design a FRET-based cAMP biosensor and use it to measure in vivodynamics of cAMP concentration changes in the sarcoplasmatic reticulum of mouse cardiomyocytes in health and disease.
- Julia U. Sprenger
- , Ruwan K. Perera
- & Viacheslav O. Nikolaev
-
Article |
Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium
Cystic fibrosis is a lethal genetic disorder commonly caused by the F508del mutation which is not amenable to gene therapy. Here, the authors use triplex-forming PNA molecules and donor DNA in biodegradable polymer nanoparticles to correct F508del and achieve clinically relevant levels of gene editing.
- Nicole Ali McNeer
- , Kavitha Anandalingam
- & Marie E. Egan
-
Article |
Design of protein switches based on an ensemble model of allostery
Protein switches have a number of potential biotechnological applications. Here, the authors present fusions of maltose-binding protein with TEM1 β-lactamase as multi-input allosteric protein switches that can be controlled by temperature and pH in the presence of the effector.
- Jay H. Choi
- , Abigail H. Laurent
- & Marc Ostermeier
-
Article
| Open AccessDesigner diatom episomes delivered by bacterial conjugation
Algae hold great promise for biofuel and chemical production but their use as model systems is hampered by the absence of suitable genetic tools. Here Karas et al. present a nuclear episomal vector for diatoms that is maintained in the absence of antibiotics, and a plasmid delivery method via conjugation with E. coli.
- Bogumil J. Karas
- , Rachel E. Diner
- & Philip D. Weyman
-
Article
| Open AccessModelling breast cancer requires identification and correction of a critical cell lineage-dependent transduction bias
Clinical breast cancers predominantly present luminal features, but experimental models are essentially basal. Here the authors show that luminal cells are significantly less susceptible to viral transduction, and present methods to analyse and overcome the bias in heterogeneous populations.
- William C. Hines
- , Paul Yaswen
- & Mina J. Bissell
-
Article |
High-throughput and quantitative assessment of enhancer activity in mammals by CapStarr-seq
Characterizing mammalian gene expression regulation by enhancer elements is complicated by the size and complexity of the genome. Here Vanhille et al.demonstrate CapStarr-Seq, a novel high-throughput method for assessing potential enhancers and deciphering the mechanisms regulating transcription
- Laurent Vanhille
- , Aurélien Griffon
- & Salvatore Spicuglia
-
Article
| Open AccessMaking water-soluble integral membrane proteins in vivo using an amphipathic protein fusion strategy
The study of integral membrane proteins (IMPs) is hampered by yields and the difficulty in retaining activity once they have been solubilized. Here Mizrachi et al. develop a strategy for in vivoexpression and solubilization of IMPs in functionally relevant states by fusing them to truncated apolipoprotein A-I.
- Dario Mizrachi
- , Yujie Chen
- & Matthew P. DeLisa
-
Article |
Metal ion-directed dynamic splicing of DNA through global conformational change by intramolecular complexation
Higher-order structured DNA molecules can be manipulated to carry out specific enzymatic functions. Here the authors demonstrate the metal ion-directed global conformational control of DNA structure, using intramolecular coordination chemistry to manipulate the DNAzyme activity.
- Toshihiro Ihara
- , Hiroyuki Ohura
- & Yusuke Kitamura
-
Article
| Open AccessA plug-and-play approach to antibody-based therapeutics via a chemoselective dual click strategy
Antibody–drug conjugates are a class of therapeutic combining the directing ability of antibodies with the cell-killing ability of cytotoxic drugs. Here the authors describe an approach based on click chemistry that enables the rapid assembly of dual-modified antibodies with potential for new therapeutic modalities.
- Antoine Maruani
- , Mark E.B. Smith
- & Stephen Caddick
-
Article
| Open AccessOn the tear resistance of skin
It is known that skin has a large tear resistance, but little is known of the mechanism behind this. Here, the authors carry out a structural analysis of rabbit skin to show how the deformation of collagen fibrils in the skin results in a strong resistance to tear propagation.
- Wen Yang
- , Vincent R. Sherman
- & Marc A. Meyers
-
Article |
Protease-degradable electrospun fibrous hydrogels
Electrospinning is a useful method of biomaterial fabrication, but a lack of bioactivity in the final construct can limit their application as mimics for biological matrices. Here, the authors fabricate a degradable electrospun scaffold as an in vitro and in vivomimic of the extracellular matrix.
- Ryan J. Wade
- , Ethan J. Bassin
- & Jason A. Burdick
-
Article |
Trehalose glycopolymer resists allow direct writing of protein patterns by electron-beam lithography
The direct-write patterning of biomolecules can yield biologically active surfaces with intricate spacing arrangements. Here, the authors show how a glycopolymer resist can stabilize many different biomolecules for patterning by electron-beam lithography.
- Erhan Bat
- , Juneyoung Lee
- & Heather D. Maynard
-
Article |
Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signalling and protein synthesis
Tumour-targeted antibodies can kill cancer cells by blocking pro-survival signalling or by delivering a toxin. Here the authors show that glypican-3 antibody fused to a bacterial toxin suppresses tumour growth more efficiently if designed to block Wnt signalling downstream of glypican-3.
- Wei Gao
- , Zhewei Tang
- & Mitchell Ho
-
Article
| Open AccessAbiotic ligation of DNA oligomers templated by their liquid crystal ordering
Some oligomers exhibit liquid-crystal-like ordering in concentrated aqueous solutions. Here, Fraccia et al. show that this kind of ordering can further facilitate DNA ligation in a way similar to a catalytic process that arises from a hierarchical self-assembly, namely liquid crystal autocatalysis.
- Tommaso P. Fraccia
- , Gregory P. Smith
- & Tommaso Bellini
-
Article
| Open AccessDemonstration of asymmetric electron conduction in pseudosymmetrical photosynthetic reaction centre proteins in an electrical circuit
Photosynthetic reaction centres have been proposed for applications in bioelectronics. Here, the authors examine electron transport through the reaction centre from R. sphaeroidesusing conductive AFM, observing asymmetric conductance along only one cofactor wire under an applied bias.
- Muhammad Kamran
- , Vincent M. Friebe
- & Michael R. Jones
-
Article
| Open AccessPredicting clinical response to anticancer drugs using an ex vivo platform that captures tumour heterogeneity
Efficacy of anticancer treatments vary across patients, imposing a need for personalized approaches. Here the authors show that responsiveness to chemotherapy can be predicted using tumour explant cultures in a patient-matched microenvironment, coupled with a machine-learning algorithm.
- Biswanath Majumder
- , Ulaganathan Baraneedharan
- & Pradip K. Majumder
-
Article |
Gene silencing by CRISPR interference in mycobacteria
Recombination-based tools for generating targeted mutations in Mycobacterium tuberculosislack efficiency. Here the authors present a CRISPR interference approach that is able to efficiently repress the expression of target genes in mycobacteria, in a rapid and cost-effective manner.
- Eira Choudhary
- , Preeti Thakur
- & Nisheeth Agarwal
-
Article |
Engineered pairs of distinct photoswitches for optogenetic control of cellular proteins
Photoreceptor-based photoswitches have proved to be powerful tools for the specific control of protein activity in live cells. Here the authors describe Magnets, a new set of photoswitches based on the Vivid photoreceptor with enhanced hetero-dimerization specificity and variable activation kinetics.
- Fuun Kawano
- , Hideyuki Suzuki
- & Moritoshi Sato
-
Article |
Defined TLR3-specific adjuvant that induces NK and CTL activation without significant cytokine production in vivo
Activation of TLRs by microbial ligands induces complex innate immune responses to activate host defence. Here the authors show that a synthetic TLR3 ligand can boost protective immunity without robust inflammatory cytokine production, minimizing toxic effects of immunization.
- Misako Matsumoto
- , Megumi Tatematsu
- & Tsukasa Seya
-
Article
| Open AccessEpigenetic and transcriptional determinants of the human breast
Epigenetic changes associated with post-natal differentiation have been characterized. Here the authors generate epigenomic and transcriptional profiles from primary human breast cells, providing insights into the transcriptional and epigenetic events that define post-natal cell differentiation in vivo.
- Philippe Gascard
- , Misha Bilenky
- & Martin Hirst
-
Article |
Hierarchical structural design for fracture resistance in the shell of the pteropod Clio pyramidata
The hierarchical structural motifs of biomaterials can lead to advantageous mechanical properties. Here, the authors reveal that a fibre-like helical structure across the shell of a planktonic pteropod suppresses crack propagation and is responsible for a high fracture resistance.
- Ling Li
- , James C. Weaver
- & Christine Ortiz
-
Article
| Open AccessDefining the phospho-adhesome through the phosphoproteomic analysis of integrin signalling
Protein phosphorylation is known to play an important role in cell adhesion signalling. Robertson et al. present a proteomic resource mapping the phosphorylation states of proteins isolated from adhesion complexes and, taking advantage of this data set, show that the cell cycle kinase CDK1 may influence cell adhesion.
- Joseph Robertson
- , Guillaume Jacquemet
- & Martin J. Humphries
-
Article
| Open AccessMechanism of erosion of nanostructured porous silicon drug carriers in neoplastic tissues
The degradation of materials used in biological applications has an important bearing on their long term performance. Here, the authors show how porous silicon nanoparticle degradation can be accelerated in vivothrough the influence of local tissue pathology, likely influencing drug delivery performance.
- Adi Tzur-Balter
- , Zohar Shatsberg
- & Natalie Artzi
-
Article |
Off-target-free gene delivery by affinity-purified receptor-targeted viral vectors
The clinical use of adeno-associated virus vectors (AAVs) has been limited by the lack of transduction specificity. Here the authors show that receptor-targeted, affinity-tagged, and purified AVVs reach tumours in mouse models with high selectivity and efficiency, outperforming therapeutic antibodies.
- Robert C. Münch
- , Anke Muth
- & Christian J. Buchholz
-
Article |
Sulphur shuttling across a chaperone during molybdenum cofactor maturation
Microbial formate dehydrogenases (FDH) are molybdenum-containing enzymes that can catalyse the reduction of CO2 into formate. Here, the authors suggest a structural and functional basis for sulphuration of the molybdenum cofactor in E. coliFDH, a key step in the production of active formate dehydrogenase.
- Pascal Arnoux
- , Christian Ruppelt
- & Anne Walburger
-
Article
| Open AccessGd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor
A metallofullerenol nanomaterial, Gd@C82(OH)22, was shown to inhibit growth of several solid cancers in preclinical models and yet exhibit low toxicity. Herein the authors show that Gd@C82(OH)22functions as an inhibitor of breast cancer stem cell function via blocking TGF-β and HIF-1α signalling, while sparing normal tissue.
- Ying Liu
- , Chunying Chen
- & Yuliang Zhao
Browse broader subjects
Browse narrower subjects
- Animal biotechnology
- Applied immunology
- Assay systems
- Biologics
- Biomaterials
- Biomimetics
- Cell delivery
- Environmental biotechnology
- Expression systems
- Functional genomics
- Gene delivery
- Gene therapy
- Genomics
- Industrial microbiology
- Metabolic engineering
- Metabolomics
- Molecular engineering
- Nanobiotechnology
- Nucleic-acid therapeutics
- Oligo delivery
- Peptide delivery
- Plant biotechnology
- Protein delivery
- Proteomics
- Regenerative medicine
- Sequencing
- Stem-cell biotechnology
- Tissue engineering