Featured
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Article
| Open AccessPoint-of-care antimicrobial coating protects orthopaedic implants from bacterial challenge
Implant infection is the most common mode of joint replacement failure with serious complications. Here, the authors report on the in vivo application of a prophylactic coating technology that can incorporate a range of antibiotics and be applied in the operating room prior to implantation.
- Weixian Xi
- , Vishal Hegde
- & Tatiana Segura
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Article
| Open AccessOne-step construction of circularized nanodiscs using SpyCatcher-SpyTag
Circularised nanodiscs (cNDs) are able to stabilise large lipid bilayer patches and are used for structural and functional studies. Current techniques to build cNDs have numerous steps and low yields; here the authors report a single step construction method using the SpyCatcher-SpyTag system.
- Shanwen Zhang
- , Qian Ren
- & Huan Bao
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Article
| Open AccessGlycan remodeled erythrocytes facilitate antigenic characterization of recent A/H3N2 influenza viruses
Here, Broszeit et al. show that circulating A/H3N2 viruses have evolved binding specificity to α2,6-sialosides on extended LacNAc moieties and therefore cannot agglutinate erythrocytes. Applying glycan remodeling allows to install functional receptors on erythrocytes and promotes identification of newly circulating variants to facilitate vaccine design.
- Frederik Broszeit
- , Rosanne J. van Beek
- & Geert-Jan Boons
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Article
| Open AccessSuppressing mosquito populations with precision guided sterile males
A. aegypti is the principal vector for arboviruses that impact on human health and wellbeing. Here the authors use precision guided sterile insect technique—pgSIT—to suppress or eliminate mosquito populations in multigeneration cage experiments.
- Ming Li
- , Ting Yang
- & Omar S. Akbari
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Article
| Open AccessTreatment of skeletal and non-skeletal alterations of Mucopolysaccharidosis type IVA by AAV-mediated gene therapy
Mucopolysaccharidosis type IVA (MPSIVA) is a lysosomal storage disorder causing severe skeletal and non-skeletal alterations in patients. Here, the authors generate a MPSIVA rat model that mimics the disabling human pathology and develop an AAV9-Galns gene therapy to treat the disease.
- Joan Bertolin
- , Víctor Sánchez
- & Fatima Bosch
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Article
| Open AccessDigital immunoassay for biomarker concentration quantification using solid-state nanopores
The concentration of a biomarker in solution can be determined by counting single molecules. Here the authors report a digital immunoassay scheme with solid-state nanopore readout to quantify a target protein and use this to measure thyroid-stimulating hormone from human serum.
- Liqun He
- , Daniel R. Tessier
- & Vincent Tabard-Cossa
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Comment
| Open AccessComputational challenges and opportunities in spatially resolved transcriptomic data analysis
Spatially resolved transcriptomic data demand new computational analysis methods to derive biological insights. Here, we comment on these associated computational challenges as well as highlight the opportunities for standardized benchmarking metrics and data-sharing infrastructure in spurring innovation moving forward.
- Lyla Atta
- & Jean Fan
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Comment
| Open AccessGrowth-coupled selection of synthetic modules to accelerate cell factory development
Synthetic biology has brought about a conceptual shift in our ability to redesign microbial metabolic networks. Combining metabolic pathway-modularization with growth-coupled selection schemes is a powerful tool that enables deep rewiring of the cell factories’ biochemistry for rational bioproduction.
- Enrico Orsi
- , Nico J. Claassens
- & Steffen N. Lindner
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Article
| Open AccessDirected evolution of prenylated FMN-dependent Fdc supports efficient in vivo isobutene production
Isobutene is a high value gaseous alkene that is widely used as fuel additive and a chemical building block. Here, the authors report an alternative pathway for isobutene bioproduction by directed evolution of prenylated FMN-dependent ferulic acid decarboxylase.
- Annica Saaret
- , Benoît Villiers
- & David Leys
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Article
| Open AccessGenetically encoded cell-death indicators (GEDI) to detect an early irreversible commitment to neurodegeneration
Cell death is a critical process in health and disease, yet available markers record later stages of cell death once a cell has already begun to decompose. Here the authors show the use of a genetically encoded calcium indicator that demarcates an irreversible stage of cell death earlier than previously possible.
- Jeremy W. Linsley
- , Kevan Shah
- & Steven Finkbeiner
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Article
| Open AccessDisrupting biological sensors of force promotes tissue regeneration in large organisms
Humans and other large mammals heal wounds by forming fibrotic scar tissue with diminished function. Here, the authors show that disrupting mechanotransduction through the focal adhesion kinase pathway in large animals accelerates healing, prevents fibrosis, and enhances skin regeneration.
- Kellen Chen
- , Sun Hyung Kwon
- & Geoffrey C. Gurtner
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Article
| Open AccessA versatile genetic engineering toolkit for E. coli based on CRISPR-prime editing
CRISPR prime editing enables double-strand break free engineering of the genome. Here the authors present a toolkit for prime editing in E. coli.
- Yaojun Tong
- , Tue S. Jørgensen
- & Sang Yup Lee
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Article
| Open AccessAging, inflammation and DNA damage in the somatic testicular niche with idiopathic germ cell aplasia
Molecular mechanisms associated with human germ cell aplasia in infertile men remain undefined. Here the authors perform single-cell transcriptome profiling to highlight differentially expressed genes and pathways in each somatic cell type in testes of men with idiopathic germ cell aplasia.
- Massimo Alfano
- , Anna Sofia Tascini
- & Andrea Salonia
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Article
| Open AccessImproved modeling of human AD with an automated culturing platform for iPSC neurons, astrocytes and microglia
Human induced pluripotent stem cell (iPSC) cells have been used to model disease in specific cell types. Here, the authors develop an automated long-term culturing platform of human iPSC neurons, astrocytes, and microglia and use it to model some cellular aspects of Alzheimer’s disease.
- Reina Bassil
- , Kenneth Shields
- & Ben Chih
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Article
| Open AccessProgrammable receptors enable bacterial biosensors to detect pathological biomarkers in clinical samples
Bacterial biosensors have promising applications in medical and environmental diagnostics. Here the authors use EMeRALD synthetic receptors to design bile salt sensors for use in liver transplant patient serum.
- Hung-Ju Chang
- , Ana Zúñiga
- & Jerome Bonnet
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Article
| Open AccessA modular self-adjuvanting cancer vaccine combined with an oncolytic vaccine induces potent antitumor immunity
Successful cancer immune therapy correlates with a T cell-inflamed tumour microenvironment. Authors show here that co-administration of a self-adjuvanting protein vaccine and an antigen-expressing oncolytic virus in an optimised regimen strongly enhances T cell immunogenicity and may turn non-inflamed tumours proinflammatory and less resistant to checkpoint blockade therapy.
- Krishna Das
- , Elodie Belnoue
- & Guido Wollmann
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Article
| Open AccessMicrobial production of megadalton titin yields fibers with advantageous mechanical properties
Here, the authors engineer microbial production of muscle titin fibers with highly desirable mechanical properties and provide structural analyses that explain the molecular mechanisms underlying high performance of this polymer with potential uses in biomedicine and textile industries, among others.
- Christopher H. Bowen
- , Cameron J. Sargent
- & Fuzhong Zhang
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Article
| Open AccessEfficient intracellular delivery of proteins by a multifunctional chimaeric peptide in vitro and in vivo
Protein delivery with cell-penetrating peptides suffers from ineffective endosomal escape and low tolerance in serum, thereby limiting treatment success. Here the authors present an intracellular protein delivery system and demonstrate efficient delivery in vitro and therapeutic efficacy in a liver failure model in vivo.
- Siyuan Yu
- , Han Yang
- & Ningshao Xia
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Article
| Open AccessA guanidine-degrading enzyme controls genomic stability of ethylene-producing cyanobacteria
The metabolic pathways used by microbes to degrade guanidine or mitigate its toxicity remain unclear. Here, the authors report a guanidine degrading enzyme that controls genomic stability of ethylene producing cyanobacterial strains.
- Bo Wang
- , Yao Xu
- & Jianping Yu
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Article
| Open AccessAn integrated in vivo/in vitro framework to enhance cell-free biosynthesis with metabolically rewired yeast extracts
Cell-free systems enable the design of biosynthetic pathways for sustainable chemical synthesis. Here the authors create an integrated framework for accelerating design using extracts from genetically rewired strains.
- Blake J. Rasor
- , Xiunan Yi
- & Michael C. Jewett
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Article
| Open AccessImplantable optical fibers for immunotherapeutics delivery and tumor impedance measurement
Immune checkpoint blockade antibodies have promising clinical applications, but suffer from severe toxicities and moderate response rates. Here the authors present an electrode-embedded, implantable optical fiber device with both local delivery and tumor impedance measurement capabilities to safely elicit durable anti-tumor immunity.
- Ai Lin Chin
- , Shan Jiang
- & Rong Tong
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Article
| Open AccessComprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions
Here, Yang et al. apply different RNA sequencing approaches to characterize the secondary structure of SARS-CoV-2 viral RNAs, report on long-range interactions along the viral genome, and uncover the virus-host RNA interactome in cells.
- Siwy Ling Yang
- , Louis DeFalco
- & Yue Wan
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Article
| Open AccessPredicting base editing outcomes with an attention-based deep learning algorithm trained on high-throughput target library screens
Base editors enable precise genetic alterations but vary in efficiency at different loci. Here the authors analyse ABEs and CBEs at over 28,000 integrated sequences to train BE-DICT, a machine learning model capable of predicting base editing outcomes.
- Kim F. Marquart
- , Ahmed Allam
- & Gerald Schwank
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Article
| Open AccessEngineered whole cut meat-like tissue by the assembly of cell fibers using tendon-gel integrated bioprinting
Mammalian cell-based cultured meat has mostly been unstructured, leaving a demand for artificial steak-like meat. Here the authors present an assembled steak-like tissue of bovine skeletal muscle, adipose tissue, and blood capillary tissue fabricated by tendon-gel integrated printing technology.
- Dong-Hee Kang
- , Fiona Louis
- & Michiya Matsusaki
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Article
| Open AccessThe landscape of alternative polyadenylation in single cells of the developing mouse embryo
Alternative polyadenylation regulates localization, half-life and translation of mRNA isoforms. Here the authors investigate alternative polyadenylation using single cell RNA sequencing data from mouse embryos and identify 3’-UTR isoforms that are regulated across cell types and developmental time.
- Vikram Agarwal
- , Sereno Lopez-Darwin
- & Jay Shendure
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Article
| Open AccessCas9-derived peptides presented by MHC Class II that elicit proliferation of CD4+ T-cells
There have been reports of immune responses against Cas9 which may impair clinical use. Here the authors scan a cohort comparable to the North American population vis-à-vis distribution of MHC-II variants to identify Cas9 peptides presented by MHC-II proteins and can stimulate CD4 + T-cells.
- Vijaya L. Simhadri
- , Louis Hopkins
- & Zuben E. Sauna
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Article
| Open AccessExpanding the binding specificity for RNA recognition by a PUF domain
The PUF RNAbinding domain has an eight-repeat structure with the ability to bind an eight-base RNA sequence. Here the authors generate a comprehensive library of variants of a PUF domain to find an RNA binding code and design PUF domains that recognize an arbitrary RNA sequence.
- Wei Zhou
- , Daniel Melamed
- & Stanley Fields
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Article
| Open AccessA non-enzymatic, isothermal strand displacement and amplification assay for rapid detection of SARS-CoV-2 RNA
The reliance on enzymes in SARS-CoV-2 RNA detection imposes limits on transport and storage conditions. Here the authors use non-enzymatic isothermal amplification to detect RNA with no need for reverse transcription.
- Mohsen Mohammadniaei
- , Ming Zhang
- & Yi Sun
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Article
| Open AccessBacterial cellulose spheroids as building blocks for 3D and patterned living materials and for regeneration
Bacterial cellulose is a promising cheap-to-produce programmable engineered living material. Here the authors present a method for production of spheroids for use as engineerable building blocks able to sense and respond to chemical inputs.
- Joaquin Caro-Astorga
- , Kenneth T. Walker
- & Tom Ellis
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Article
| Open AccessSCOPE enables type III CRISPR-Cas diagnostics using flexible targeting and stringent CARF ribonuclease activation
Type III CRISPR-Cas systems recognize and cleave target RNAs and produce signalling molecules. Here the authors discover that both processes are governed by a flexible seed region, ultimately resulting in SCOPE, a SARSCoV-2 diagnostic assay with atto-molar sensitivity.
- Jurre A. Steens
- , Yifan Zhu
- & Raymond H. J. Staals
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Article
| Open AccessIntegration of FRET and sequencing to engineer kinase biosensors from mammalian cell libraries
Existing Förster Resonance Energy Transfer (FRET) biosensors are often limited in their sensitivity. Here the authors report FRET-seq which they use to identify Fyn and ZAP70 kinase biosensors with enhanced performance, and use them to image T-cell activation and screen drugs.
- Longwei Liu
- , Praopim Limsakul
- & Yingxiao Wang
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Article
| Open AccessGrafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture
Tendon self-renewal occurs rarely and reconstructive surgery comes with significant limitations. Here the authors present an induced pluripotent stem cell-based method to generate tenocytes, analyze their developmental trajectory using scRNA-seq, and demonstrate their contribution to motor function recovery after Achilles tendon injury via engraftment and paracrine effects.
- Taiki Nakajima
- , Akihiro Nakahata
- & Makoto Ikeya
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Article
| Open AccessLive cell tagging tracking and isolation for spatial transcriptomics using photoactivatable cell dyes
Spatial transcriptomics aims to pair omic data with tissue structure. Here the authors report Spatially PhotoActivatable Colour Encoded Cell Address Tags (SPACECAT) to track and isolate live cells by location; this enables spatially informed downstream assays like scRNA-seq and flow cytometry.
- Alex S Genshaft
- , Carly G. K. Ziegler
- & Alex K. Shalek
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Article
| Open AccessComplete and efficient conversion of plant cell wall hemicellulose into high-value bioproducts by engineered yeast
Cellulosic hydrolysates contain substantial amounts of acetate, which is toxic to fermenting microorganisms. Here, the authors engineer Baker’s yeast to co-consume xylose and acetate for triacetic acid lactone production from a hemicellulose hydrolysate of switchgrass.
- Liang Sun
- , Jae Won Lee
- & Yong-Su Jin
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Article
| Open AccessEn route to dynamic life processes by SNARE-mediated fusion of polymer and hybrid membranes
A variety of artificial cells springs from the functionalization of liposomes with proteins but these models suffer from low durability without repair and replenishment mechanisms. Here, the authors show that synthetic amphiphile membranes undergo SNARE-mediated fusion, and determine bending rigidity and pore edge tension as key parameters for fusion.
- Lado Otrin
- , Agata Witkowska
- & Tanja Vidaković-Koch
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Article
| Open AccessSpatiotemporally-resolved mapping of RNA binding proteins via functional proximity labeling reveals a mitochondrial mRNA anchor promoting stress recovery
Proximity labeling is used to map and discover proteins in specific subcellular compartments. Here the authors combine APEX-mediated proximity labeling with organic-aqueous phase separation to identify nuclear, nucleolar, and outer mitochondrial membrane RNA binding proteins.
- Wei Qin
- , Samuel A. Myers
- & Alice Y. Ting
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Article
| Open AccessMeasuring expression heterogeneity of single-cell cytoskeletal protein complexes
Existing methods for multimeric protein complex quantification in single cells suffer from limited selectivity and sensitivity. Here the authors report Single-cell protein Interaction Fractionation Through Electrophoresis and immunoassay Readout (SIFTER) and use this to probe the effects of cellular stress.
- Julea Vlassakis
- , Louise L. Hansen
- & Amy E. Herr
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Article
| Open AccessGenome-scale target identification in Escherichia coli for high-titer production of free fatty acids
Identification of gene targets is one of the major challenges to construct superior microbial cell factory for chemical synthesis. Here, the authors employ CRISPRi and omics analyses for genome-scale target genes identification for high-titer production of free fatty acids in E. coli.
- Lixia Fang
- , Jie Fan
- & Hao Song
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Article
| Open AccessElectrophysiological engineering of heart-derived cells with calcium-dependent potassium channels improves cell therapy efficacy for cardioprotection
Strategies to improve the function of damaged hearts with progenitor cells have stalled. Here, the authors show that gene transfer of a calcium-dependent potassium channel enhances the functional properties and ability of explant-derived cells to improve heart function after a heart attack.
- Patrick Vigneault
- , Sandrine Parent
- & Stanley Nattel
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Article
| Open AccessMirtron-mediated RNA knockdown/replacement therapy for the treatment of dominant retinitis pigmentosa
Rhodopsin-related dominant retinitis pigmentosa is a degenerative disease of the retina of the eye for which there is no current treatment. In this study, the authors use a novel form of RNA-interference- artificial mirtrons- to slow retinal degeneration in a mouse model of the disease.
- Harry O. Orlans
- , Michelle E. McClements
- & Robert E. MacLaren
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Article
| Open AccessMetabolome and proteome analyses reveal transcriptional misregulation in glycolysis of engineered E. coli
Synthetic pathways represent a metabolic burden on host cells. Here the authors engineer Cra-binding sites to prevent misregulation in glycerol and carotenoid overproducing E. coli strains.
- Chun-Ying Wang
- , Martin Lempp
- & Hannes Link
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Article
| Open AccessCRISPR-Cas9 globin editing can induce megabase-scale copy-neutral losses of heterozygosity in hematopoietic cells
CRISPR-Cas9 generates double-strand breaks, which pose a threat to genome integrity. Here the authors show loss of heterozygosity in edited hematopoietic progenitor cells.
- J. Boutin
- , J. Rosier
- & A. Bedel
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Article
| Open AccessOptimization of C-to-G base editors with sequence context preference predictable by machine learning methods
C->G transversions can be highly desirable editing outcomes. Here the authors optimise CGBEs and provide a deep learning model for predicting editing outcomes based on sequence context.
- Tanglong Yuan
- , Nana Yan
- & Erwei Zuo
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Article
| Open AccessDendrimer end-terminal motif-dependent evasion of human complement and complement activation through IgM hitchhiking
Understanding nanomaterials interactions with complement is important for a number of applications. Here, the authors study the interaction of sub 6 nm dendrimers with complement and show the small dendrimers escape complement activation but do interact with IgM to trigger lectin-pathway complement activation.
- Lin-Ping Wu
- , Mario Ficker
- & Seyed M. Moghimi
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Article
| Open AccessNanopore sequencing of brain-derived full-length circRNAs reveals circRNA-specific exon usage, intron retention and microexons
Short-read sequencing methods cannot delineate internal exon composition and alternative splicing events of long and multi-exon circular RNAs (circRNAs). Here the authors provide a global map of full-length circRNAs by long-read sequencing in human and mouse brain samples.
- Karim Rahimi
- , Morten T. Venø
- & Jørgen Kjems
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Article
| Open AccessTracking the introduction and spread of SARS-CoV-2 in coastal Kenya
SARS-CoV-2 was first detected in Kenya in March 2020 and there was evidence of local transmission in the following months. Here, the authors characterise the early stages of the epidemic in coastal Kenya using phylogenetics and find evidence of multiple strain importations from international points of entry.
- George Githinji
- , Zaydah R. de Laurent
- & Charles N. Agoti
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Article
| Open AccessAn engineered IL-2 reprogrammed for anti-tumor therapy using a semi-synthetic organism
The use of synthetic organisms could provide opportunities for discovery and advanced manufacturing of medical drugs. Here the authors use a semi-synthetic organism with an expanded genetic code to generate site-specific chemical modifications in human IL-2.
- Jerod L. Ptacin
- , Carolina E. Caffaro
- & Marcos E. Milla
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Article
| Open Accessm6Am-seq reveals the dynamic m6Am methylation in the human transcriptome
m6Am is a dynamic and reversible RNA modification found on the mRNA cap. Here the authors report m6Am-seq to directly distinguish m6Am from m6A and identify functional methylation sites.
- Hanxiao Sun
- , Kai Li
- & Chengqi Yi
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Article
| Open AccessSynergistic effect of tumor chemo-immunotherapy induced by leukocyte-hitchhiking thermal-sensitive micelles
Targeting the adenosinergic pathway represents a therapeutic option to overcome tumor-induced immunosuppression. Here the authors design E-selectin-modified thermal-sensitive micelles loaded with doxorubicin and an adenosine A2 receptor antagonist to enhance chemotherapy-induced anti-tumor immune responses.
- Jing Qi
- , Feiyang Jin
- & Yongzhong Du
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