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| Open AccessBionic artificial skin with a fully implantable wireless tactile sensory system for wound healing and restoring skin tactile function
Although artificial skins can facilitate the healing of damaged skin, the restoration of tactile functions remain a challenge. Here, Kang et al. report an artificial skin with an implantable tactile sensor that can simultaneously replace the tactile function by nerve stimulation and promote skin regeneration.
- Kyowon Kang
- , Seongryeol Ye
- & Youngmee Jung
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Article
| Open AccessCultured meat with enriched organoleptic properties by regulating cell differentiation
Achieving organoleptic properties of conventional meat is important for cultured meat production. Here, the authors demonstrate that the texture, flavor, and nutritional content of cultured meat can be significantly enhanced by regulating cell differentiation inside hydrogel scaffolds.
- Milae Lee
- , Sohyeon Park
- & Jinkee Hong
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Article
| Open AccessHigh throughput intracellular delivery by viscoelastic mechanoporation
Scalability of mechanoporation strategies for intracellular delivery remains challenging. Here, the authors demonstrate a microfluidic approach for delivering mRNA and CRISPR-Cas systems to over 250 million cells per minute.
- Derin Sevenler
- & Mehmet Toner
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Article
| Open AccessOptogenetic spatial patterning of cooperation in yeast populations
Microbial communities are the siege of complex metabolic interactions including cooperation and competition. Here, the authors report the utilization of optogenetics and spatial light-patterning to activate the expression of the invertase SUC2 at selected locations and selectively switch cooperation and competition roles of the yeast cells.
- Matthias Le Bec
- , Sylvain Pouzet
- & Pascal Hersen
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Article
| Open AccessHuman apical-out nasal organoids reveal an essential role of matrix metalloproteinases in airway epithelial differentiation
Airway organoids made in Matrigel are in basal-out orientation. Here, authors present apical-out nasal organoids using a biochemically defined hydrogel system, revealing that matrix metalloproteinases are required for normal epithelial development.
- Liyue Li
- , Linyi Jiao
- & Chunwei Li
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Article
| Open AccessMammalian cell growth characterisation by a non-invasive plate reader assay
Automated and non-invasive mammalian cell analysis is currently lagging behind due to a lack of methods suitable for a variety of cell lines and applications. Here the authors develop a high throughput non-invasive method for tracking suspension and adhesion mammalian cell growth based on plate reader measures to characterize engineered cell lines.
- Alice Grob
- , Chiara Enrico Bena
- & Francesca Ceroni
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Article
| Open AccessTransient inhibition of 53BP1 increases the frequency of targeted integration in human hematopoietic stem and progenitor cells
Here the authors demonstrate that the frequency of HDR in human hematopoietic stem and progenitor cells is increased by the delivery of an inhibitor of 53BP1 as a recombinant peptide. This approach is applicable for a variety of therapeutically relevant loci in HSPCs as well in other primary human cell types.
- Ron Baik
- , M. Kyle Cromer
- & Matthew H. Porteus
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Article
| Open AccessACIDES: on-line monitoring of forward genetic screens for protein engineering
Screening mutated proteins is a versatile strategy in protein research, producing massive datasets when combined with NGS. Here, authors present ACIDES to estimate mutated protein fitness and aid protein engineering pipelines in a range of applications, including gene therapy.
- Takahiro Nemoto
- , Tommaso Ocari
- & Ulisse Ferrari
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Article
| Open AccessCharacterizations of a neutralizing antibody broadly reactive to multiple gluten peptide:HLA-DQ2.5 complexes in the context of celiac disease
Targeting gluten antigens presents a plausible therapy option for celiac disease. Here the authors generate and characterize a broadly neutralizing antibody recognizing more than 25 gluten peptide:HLA-DQ2.5 complexes, with structural analyses implicating its mode of interaction, and with mouse in vivo studies supporting its therapeutic feasibility.
- Yuu Okura
- , Yuri Ikawa-Teranishi
- & Tomoyuki Igawa
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Article
| Open AccessRedox-enabled electronic interrogation and feedback control of hierarchical and networked biological systems
With redox-linked synthetic biology and electrobiofabrication, electronic information can be transmitted in a bidirectional manner between biology and electronics. Here the authors design an electrogenetic platform that allows real time electronic control of biological functions from proteins and gene circuits to cell consortia.
- Sally Wang
- , Chen-Yu Chen
- & William E. Bentley
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Article
| Open AccessBuilding synthetic chromosomes from natural DNA
Building synthetic chromosomes from natural components is an unexplored alternative to de novo chromosome synthesis that may have many potential applications. In this paper, the authors report CReATiNG, a method for constructing synthetic chromosomes from natural components in yeast.
- Alessandro L. V. Coradini
- , Christopher Ne Ville
- & Ian M. Ehrenreich
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Article
| Open AccessEngineering a synthetic energy-efficient formaldehyde assimilation cycle in Escherichia coli
One-carbon substrates are attractive feedstocks for circular bioeconomy. Here, the authors design an erythrulose monophosphate (EuMP) cycle for formaldehyde assimilation, demonstrate the activity of the core reactions in E. coli, and show its integration with pathway reactions existed in pentose phosphate pathway and glycolysis.
- Tong Wu
- , Paul A. Gómez-Coronado
- & Hai He
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Article
| Open AccessDeciphering driver regulators of cell fate decisions from single-cell transcriptomics data with CEFCON
Deciphering the roles of gene regulation in cell fate decisions is crucial. Here, authors present CEFCON, a network-based framework that reveals cell-lineage-specific gene regulatory networks and identifies driver regulators controlling cell fate decisions from single-cell transcriptomics data.
- Peizhuo Wang
- , Xiao Wen
- & Jianyang Zeng
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Article
| Open AccessReconfiguration of the reductive TCA cycle enables high-level succinic acid production by Yarrowia lipolytica
Redox imbalance limits succinic acid (SA) biosynthesis from glucose via the reductive tricarboxylic acid (TCA) cycle in yeast. Here, the authors engineering the aerobic yeast Yarrowia lipolytica for efficient SA production without pH control via coupling the oxidative and reductive TCA cycle for NADH regeneration in mitochondria.
- Zhiyong Cui
- , Yutao Zhong
- & Qingsheng Qi
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Article
| Open AccessOptimized design and in vivo application of optogenetically functionalized Drosophila dopamine receptors
Designing optogenetically functionalized G protein-coupled receptors (optoXRs) to mimic endogenous signaling in vivo is challenging. Here, the authors optimize the design of optoXRs by considering evolutionary conserved protein interactions, and they employ this approach in fruit flies.
- Fangmin Zhou
- , Alexandra-Madelaine Tichy
- & Peter Soba
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Article
| Open AccessHigh resolution mapping of the tumor microenvironment using integrated single-cell, spatial and in situ analysis
The integration of single-cell and spatial data can provide a more comprehensive picture of the network of cells within the tumour microenvironment. Here the authors use a combination of single-cell and spatial technologies including 10x Xenium to characterise serial formalin-fixed, paraffin-embedded human breast cancer sections.
- Amanda Janesick
- , Robert Shelansky
- & Sarah E. B. Taylor
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Review Article
| Open AccessCustomizing cellular signal processing by synthetic multi-level regulatory circuits
As synthetic biology permeates society, the signal processing circuits in engineered living systems must be customized to meet practical demands. In this review, the authors outline design strategies for the DNA, RNA, and protein-level circuits and the hybrid “multi-level” circuits.
- Yuanli Gao
- , Lei Wang
- & Baojun Wang
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Article
| Open AccessPathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity
Clustering-based analysis has limited power in highly dynamic single-cell data, which is a common situation in tumour samples. Here, authors introduce GSDensity, enabling pathway-centric analysis for the direct integration of data with their domain knowledge.
- Qingnan Liang
- , Yuefan Huang
- & Ken Chen
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Article
| Open AccessIntranasal mask for protecting the respiratory tract against viral aerosols
The spread of many infectious diseases substantially relies on aerosol transmission to the respiratory tract. Here, the authors design an intranasal mask with the ability to intercept viral aerosols, entrap and inactivate virus, thus preventing respiratory tract infection.
- Xiaoming Hu
- , Shuang Wang
- & Wei Wei
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Article
| Open AccessSoft ferroelectret ultrasound receiver for targeted peripheral neuromodulation
Neurostimulators are often bulky and uncomfortable. Researchers report a wireless, leadless, and battery-free ultrasound receiver that wraps around the target peripheral nerve and allows precise modulation of organ function, providing a framework for future bioelectronic medicines
- Tong Li
- , Zhidong Wei
- & Zhang-Qi Feng
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Article
| Open AccessWhole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma
Current sequencing technologies can shed light on the stepwise progression of lung adenocarcinoma. Here, the authors characterize tumor progression in lung adenocarcinomas from an early stage using short and long read whole-genome sequencing, bulk and spatial transcriptomics, and epigenomics.
- Yasuhiko Haga
- , Yoshitaka Sakamoto
- & Ayako Suzuki
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Q&A
| Open AccessA conversation about cultivated meat
Summary: Cultivated or cultured meat is promising to revolutionize the food industry in the coming years to decades, helping to resolve concerns related to the environmental impact and ethical implications linked to conventional meat production. We talked to Dr. Sandhya Sriram, the Group CEO and Co-founder of Shiok Meats Pte. Ltd., Singapore; Prof. Shulamit Levenberg, the former Dean of the Biomedical Engineering Department at the Technion, current Director of the Technion Center for 3D Bioprinting and The Rina & Avner Schneur Center for Diabetes Research, as well as the Co-founder and Chief Scientific Adviser of Aleph Farms, Israel; and Dr. Timothy Olsen, Head of Cultured Meat in the Life Science business at Merck KGaA, Germany; about this relatively new and quickly developing sector. They explain what their teams are working on, including the biggest recent accomplishments, speak about the main challenges facing the field and how they can be resolved, and share their visions about the future of cultivated meat, aiming to provide more equitable and sustainable access to nutritious food for the growing world population.
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Article
| Open AccessInduced formation of primordial germ cells from zebrafish blastomeres by germplasm factors
Primordial germ cell (PGC) transplantation is an important technology for developmental biology and genetic breeding. Here, Wang et al. develop an approach for PGC induction that enhances the efficiency of PGC transplantation in zebrafish.
- Xiaosi Wang
- , Junwen Zhu
- & Yonghua Sun
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Article
| Open AccessAtherosclerotic plaque development in mice is enhanced by myeloid ZEB1 downregulation
Accumulation of lipid-laden macrophages in the arterial wall is a critical step in atherosclerosis. Here, the authors show that downregulation of Zeb1 in macrophages promotes lipid accumulation and atherosclerotic plaque formation while its restoration with macrophage-targeted nanoparticles reverses these effects.
- M. C. Martinez-Campanario
- , Marlies Cortés
- & Antonio Postigo
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Article
| Open AccessSingle-cell spatial metabolomics with cell-type specific protein profiling for tissue systems biology
The authors developed a framework for joint protein-metabolite profiling at the single-cell level in human tissue combining targeted multiplexed protein imaging and untargeted spatial metabolomics in a single pipeline.
- Thomas Hu
- , Mayar Allam
- & Ahmet F. Coskun
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Article
| Open AccessGNTD: reconstructing spatial transcriptomes with graph-guided neural tensor decomposition informed by spatial and functional relations
Reconstructing transcriptome-wide spatially-resolved gene expressions requires modelling nonlinear patterns and spatial structures in RNA profiling data. Here, authors introduce a graph-guided neural hierarchical tensor decomposition model that incorporates spatial and functional relations for the task.
- Tianci Song
- , Charles Broadbent
- & Rui Kuang
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Article
| Open AccessAnti-VEGFR2 F(ab′)2 drug conjugate promotes renal accumulation and glomerular repair in diabetic nephropathy
Poor renal distribution of antibody-based drugs limits the treatment efficiency for diabetic nephropathy and causes side effects. Here, the authors prepare an antibody fragment drug conjugate, antiVEGFR2 F(ab′)2-SS31, improving renal distribution and meriting drug validation in diabetic nephropathy therapy.
- Di Liu
- , Yanling Song
- & Yongzhong Du
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Article
| Open AccessA patterned human primitive heart organoid model generated by pluripotent stem cell self-organization
Pluripotent stem cell-derived organoids can recapitulate significant hallmarks of human organ development and are becoming critical tools for human research. Here, the authors report significant technical steps for generating sophisticated synthetic human primitive heart organoids.
- Brett Volmert
- , Artem Kiselev
- & Aitor Aguirre
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Article
| Open AccessUniKP: a unified framework for the prediction of enzyme kinetic parameters
Prediction of enzyme kinetic parameters is essential for designing and optimising enzymes for various biotechnological and industrial applications. Here, authors presented a prediction framework (UniKP), which improves the accuracy of predictions for three enzyme kinetic parameters.
- Han Yu
- , Huaxiang Deng
- & Xiaozhou Luo
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Article
| Open AccessGeneration of three-dimensional meat-like tissue from stable pig epiblast stem cells
Cultured meat technology promises to alleviate protein shortages, but still faces many challenges. Here, the authors achieve serum-free myogenic differentiation of porcine pre-gastrulation epiblast stem cells and generate meat-like tissue via edible plant-based scaffolds without any animal compounds.
- Gaoxiang Zhu
- , Dengfeng Gao
- & Jianyong Han
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Article
| Open AccessAmplified fluorogenic immunoassay for early diagnosis and monitoring of Alzheimer’s disease from tear fluid
Accurate diagnosis of Alzheimer’s disease in its earliest stage can prevent the disease and delay the symptoms. Here the authors identify a potential Alzheimer’s biomarker from tear fluid, and develop a nanoparticle-based immunoassay for its detection, demonstrating potential in Alzheimer’s diagnosis.
- Sojeong Lee
- , Eunjung Kim
- & Seungjoo Haam
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Article
| Open AccessSTalign: Alignment of spatial transcriptomics data using diffeomorphic metric mapping
Spatial transcriptomics (ST) enables gene expression characterisation within tissue sections, but comparing across sections and technologies remains challenging. Here, authors develop STalign to spatially align ST data and demonstrate applications including aligning to common coordinate frameworks.
- Kalen Clifton
- , Manjari Anant
- & Jean Fan
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Article
| Open AccessFunctional and analytical recapitulation of osteoclast biology on demineralized bone paper
Here, authors report demineralized bone paper-based in vitro osteogenic culture and assay platforms that replicate essential bone tissue complexity, osteoclast processes, and drug responses with high fidelity and predictive power.
- Yongkuk Park
- , Tadatoshi Sato
- & Jungwoo Lee
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Article
| Open AccessSaturation genome editing of DDX3X clarifies pathogenicity of germline and somatic variation
Pathogenic variants of DDX3X are associated with neurodevelopmental disorders (NDD) and cancer. Here, the authors perform saturation genome editing of DDX3X to test the functional impact of 12,776 variants, develop a machine learning classifier to identify variants relevant for NDD, and show that DDX3X predominantly acts as a tumour suppressor in cancer.
- Elizabeth J. Radford
- , Hong-Kee Tan
- & Matthew E. Hurles
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Article
| Open AccessSystemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function
A systemically administered peptide (CARSKNKDC) that homes to injured tissues, has inherent ability to promote wound healing. Here, the authors show that this peptide binds to syndecan-4 and activates ARF6 to trigger re-epithelialisation and the naturally occurring wound repair pathway.
- Horacio Maldonado
- , Bryan D. Savage
- & Tero A. H. Järvinen
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Article
| Open AccessANCA: artificial nucleic acid circuit with argonaute protein for one-step isothermal detection of antibiotic-resistant bacteria
Antibiotic-resistant bacteria pose a growing threat to global health. Here, the authors present an artificial nucleic acid circuit with argonaute protein (ANCA) for one-step, amplification-free, and isothermal detection of carbapenemase-producing Klebsiella pneumoniae.
- Hyowon Jang
- , Jayeon Song
- & Taejoon Kang
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Article
| Open AccessSecretory GFP reconstitution labeling of neighboring cells interrogates cell–cell interactions in metastatic niches
Methodologies to study the mechanisms of cell–cell interactions in metastatic niches remain scarce. Here, the authors develop a secretory GFP reconstitution-based system to tag tissue-resident cells neighboring on cancer cells within the metastatic niche.
- Misa Minegishi
- , Takahiro Kuchimaru
- & Satoshi Nishimura
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Article
| Open AccessMetabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines
Extracellular vesicles (EVs) have been actively explored for diagnostic and therapeutic applications. Here, the authors report a universal metabolic tagging technology to generate chemically tagged EVs from parent cells, modulate EV-cell interactions, and develop potent EV-based cancer vaccines.
- Rimsha Bhatta
- , Joonsu Han
- & Hua Wang
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Article
| Open AccessEngineering artificial photosynthesis based on rhodopsin for CO2 fixation
Microbial rhodopsins are major contributors to global light harvesting on Earth, but their role in carbon fixation is unclear. Here, the authors construct an artificial photosynthesis system by combining rhodopsin with an extracellular electron uptake mechanism for photoelectrosynthetic CO2 fixation in Ralstonia eutropha.
- Weiming Tu
- , Jiabao Xu
- & Wei E. Huang
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Article
| Open AccessDynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry
Off-target toxicity of antisense oligonucleotides (ASOs) poses a challenge for their clinical use. Here, authors develop a toehold-bearing ASO architecture that mitigates a broad spectrum of off-target interactions, significantly enhancing the safety profile of ASO drugs.
- Chisato Terada
- , Kaho Oh
- & Tsuyoshi Yamamoto
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Article
| Open AccessFully implanted battery-free high power platform for chronic spinal and muscular functional electrical stimulation
Electrical stimulation of the neuromuscular system holds promise for therapeutic biomedical applications, but is currently restricted by power. Here, the authors introduce fully implantable resonator-based designs achieving ±20 V compliance and >300 mW output, enabling multichannel, biphasic, current-controlled operation to evoke functional gate patterns for 6-weeks in freely behaving rats.
- Alex Burton
- , Zhong Wang
- & Philipp Gutruf
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Article
| Open AccessEngineered immunogens to elicit antibodies against conserved coronavirus epitopes
A pan-betacoronavirus vaccine will likely require the elicitation of antibodies against spike regions conserved across diverse coronaviruses. Here, authors computationally engineer and experimentally validate immunogens to elicit antibodies against two such spike regions.
- A. Brenda Kapingidza
- , Daniel J. Marston
- & Mihai L. Azoitei
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Article
| Open AccessXylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid production
It’s challenging to produce natural products using single strains of engineered microbes fed by renewable carbon sources. Here, the authors assemble a microbial consortium consisting of engineered S. stipitis and S. cerevisiae for streamlined production of (S)-norcoclaurine from glucose and xylose simultaneously.
- Meirong Gao
- , Yuxin Zhao
- & Zengyi Shao
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Article
| Open AccessInterrogating ligand-receptor interactions using highly sensitive cellular biosensors
The interaction of membrane-resident proteins plays an essential role in biological processes. Here the authors describe cellular biosensors based on chimeric receptors, as a tool to study the interaction of receptor-ligand pairs such as immune checkpoint molecules or virus attachment proteins and their receptors.
- Maximilian A. Funk
- , Judith Leitner
- & Peter Steinberger
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Article
| Open AccessLocal H2 release remodels senescence microenvironment for improved repair of injured bone
Senescence microenvironment inhibits tissue repair in elderly individuals. Here, the authors demonstrate that local H2 supply has anti-inflammation and anti-senescence effects, and develop a H2-releasing scaffold to enhance aging bone defect repair.
- Shengqiang Chen
- , Yuanman Yu
- & Qianjun He
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Article
| Open AccessDetection of isoforms and genomic alterations by high-throughput full-length single-cell RNA sequencing in ovarian cancer
Long-read single-cell RNA sequencing is capable of detecting isoform-level gene expression and genomic alterations such as mutations and gene fusions, thereby providing cell-specific genotype-phenotype information. Here, the authors use long-read scRNA-seq on metastatic ovarian cancer samples and detect cell-type specific isoforms and gene fusions that may otherwise be misclassified in short-read data.
- Arthur Dondi
- , Ulrike Lischetti
- & Niko Beerenwinkel
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Article
| Open AccessA simeprevir-inducible molecular switch for the control of cell and gene therapies
Chemical inducer of dimerization (CID) modules can be used to effectively control biological processes; however, CID modules have been explored primarily in engineering cells for in vitro applications using inducers that have limited clinical utility. Here, the authors identify a CID module with favorable properties to enable rapid translation from in vitro applications to potential use in humans.
- Stacey E. Chin
- , Christina Schindler
- & Natalie J. Tigue
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Article
| Open AccessDiscovery and remodeling of Vibrio natriegens as a microbial platform for efficient formic acid biorefinery
Formic acid (FA) is a promising CO2-equivalent feedstock for onecarbon biorefinery, but microbial host that can efficiently utilize FA is unavailable. Here, the authors engineer a non-native closed loop in Vibrio natriegens and demonstrate its application in promoting FA utilization.
- Jinzhong Tian
- , Wangshuying Deng
- & Yang Gu
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Article
| Open AccessUltra-durable cell-free bioactive hydrogel with fast shape memory and on-demand drug release for cartilage regeneration
Achieving successful in vivo cartilage regeneration remains challenging. Here they present a cell-free, multiple hydrogen-bond crosslinked hydrogel loaded with tannic acid and Kartogenin with ultra-durable mechanical properties and stage-dependent drug release behavior to promote cartilage regeneration.
- Yuxuan Yang
- , Xiaodan Zhao
- & Xuesi Chen
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