Featured
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Article
| Open AccessImaging cellular forces with photonic crystals
Current techniques for visualizing cell generated forces suffer from throughput limitations. Here, Gu et al. introduced photonic crystal cellular force microscopy, inspired by chameleons, enabling visualization and quantification of vertically directed cell forces, well-suited for drug screening.
- Qiwei Li
- , Zaozao Chen
- & Zhongze Gu
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Article
| Open AccessSingle amino acid change alters specificity of the multi-allelic wheat stem rust resistance locus SR9
Among all wheat rust resistance genes, SR9 has the largest number of alleles. Here, the authors use gene cloning, complementation and comparative genetics to resolve the relationship among Sr9 alleles, confirm their allelic identities, and show that a single amino acid change leads to resistance to Ug99.
- Jianping Zhang
- , Jayaveeramuthu Nirmala
- & Evans Lagudah
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Article
| Open AccessEnhanced pericyte-endothelial interactions through NO-boosted extracellular vesicles drive revascularization in a mouse model of ischemic injury
Treatment alternatives are not available for a significant portion of critical limb ischemia patients. Here, the authors show a strategy to engineer mesenchymal stem cells-derived extracellular vesicles to induce revascularization in mice.
- Ling Guo
- , Qiang Yang
- & Min Feng
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Article
| Open AccessEmergence of task-related spatiotemporal population dynamics in transplanted neurons
Cell therapy is a promising treatment for brain injury, but it is unclear if transplanted neurons demonstrate population dynamics. By monitoring transplanted neurons in injured mice, here the authors show the emergence of dynamics resembling intact networks.
- Harman Ghuman
- , Kyungsoo Kim
- & Karunesh Ganguly
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Article
| Open AccessDiatomic iron nanozyme with lipoxidase-like activity for efficient inactivation of enveloped virus
Enveloped viruses encased within a lipid bilayer membrane are highly contagious and cause diseases like influenza and COVID-19, so strategies for their prevention and inactivation are needed. Here, the authors develop a diatomic iron nanozyme with lipoxidase-like activity for the inactivation of enveloped viruses, where the diatomic iron sites destroy the viral envelope via lipid peroxidation.
- Beibei Li
- , Ruonan Ma
- & Yadong Li
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Article
| Open AccessAn on-demand bioresorbable neurostimulator
Despite promising advantages, bioresorbable electronics face practical limitations due to unpredictable device lifetimes. Here, the authors introduce an on-demand bioresorbable neurostimulator powered by biosafe ultrasound to treat peripheral nerve injury and neuropathies.
- Dong-Min Lee
- , Minki Kang
- & Sang-Woo Kim
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Article
| Open AccessLung SORT LNPs enable precise homology-directed repair mediated CRISPR/Cas genome correction in cystic fibrosis models
Roughly 10% of Cystic Fibrosis (CF) patients still have no effective medicine to take. Lung Selective Organ Targeting (SORT) Lipid Nanoparticles can efficiently deliver Cas9 mRNA, sgRNA, and donor ssDNA templates for precise homology-directed repair-mediated gene correction in ex vivo and in vivo CF models.
- Tuo Wei
- , Yehui Sun
- & Daniel J. Siegwart
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Article
| Open AccessEngineering sulfonate group donor regeneration systems to boost biosynthesis of sulfated compounds
Sufficient supply of sulfonate group donor is critical to biomanufacturing of the sulfate containing compounds. Here, the authors engineer two sulfonate group donor regeneration systems, including 3'-phosphoadenosine-5'-phosphosulfate and the newly discovered 5'-phosphosulfate, to boost biosynthesis of sulfated compounds.
- Ruirui Xu
- , Weijao Zhang
- & Zhen Kang
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Article
| Open AccessA statistical framework for differential pseudotime analysis with multiple single-cell RNA-seq samples
Pseudotime analysis is prevalent in single-cell RNA-seq, but it remains challenging to perform it across multiple samples and experimental conditions. Here, the authors develop Lamian, a computational framework for multi-sample pseudotime analysis that adjusts for biological and technical variation to detect gene program changes along cell trajectories and across conditions.
- Wenpin Hou
- , Zhicheng Ji
- & Hongkai Ji
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Article
| Open AccessNULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing
Unlocking the blood proteome requires exquisite sensitivity and multiplexing to detect low and high abundance proteins simultaneously. Here the authors describe a 200-plex immunoassay with attomolar sensitivity to detect important low abundance proteins in inflammatory diseases and COVID-19.
- Wei Feng
- , Joanne C. Beer
- & Xiao-Jun Ma
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Article
| Open AccessSphingomyelin-derived nanovesicles for the delivery of the IDO1 inhibitor epacadostat enhance metastatic and post-surgical melanoma immunotherapy
Epacadostat is a selective IDO1 inhibitor shown to promote anti-tumor immune responses in preclinical models, however it has failed in a Phase III clinical trial for treating metastatic melanoma. Here the authors design a sphingomyelin-derived nanovesicle system for epacadostat delivery with improved pharmacokinetics and anti-tumor activity when combined with a PD-1 inhibitor in melanoma preclinical models.
- Zhiren Wang
- , Wenpan Li
- & Jianqin Lu
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Article
| Open AccessAdoptive macrophage directed photodynamic therapy of multidrug-resistant bacterial infection
There is increased demand for effective, broad-spectrum treatment options against severe, multi-drug resistant bacterial infections. Here, Wang et al describe an effective photodynamic therapy based on the adoptive transfer of macrophages loaded with a lysosomal photosensitiser.
- Zehui Wang
- , Anhua Wu
- & Yi Xiao
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Article
| Open AccessElectrocatalytic on-site oxygenation for transplanted cell-based-therapies
Oxygen is the most limiting factor in cell transplantation. Here, the authors present an on-site oxygen production platform for implantable cell therapeutics via electrocatalytic water electrolysis, demonstrating the maintenance of high cell loading in hypoxic incubation and a rat model.
- Inkyu Lee
- , Abhijith Surendran
- & Tzahi Cohen-Karni
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Article
| Open AccessCoordinated regulation of the entry and exit steps of aromatic amino acid biosynthesis supports the dual lignin pathway in grasses
The study by El-Azaz et al. uncovers how grasses fine-tune tyrosine and phenylalanine production to support their unique dual entry pathway to lignin and phenylpropanoids. The findings help improve sustainable production of aromatic chemicals in crops.
- Jorge El-Azaz
- , Bethany Moore
- & Hiroshi A. Maeda
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Article
| Open AccessRational design of microRNA-responsive switch for programmable translational control in mammalian cells
Artificial regulation of translation by intracellular RNAs has many potential applications. Here, authors design a platform capable of miRNA-triggered upregulation or downregulation using a single RNA construct, and demonstrate its use in constructing logic gates and cell-type classifiers.
- Hui Ning
- , Gan Liu
- & Zhen Xie
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Article
| Open AccessCell-free biosynthesis combined with deep learning accelerates de novo-development of antimicrobial peptides
Deep learning holds a great promise for the discovery and design of bioactive peptides, but experimental approaches to validate candidates in high throughput and at low cost are needed. Here, the authors combine deep learning and cell free biosynthesis for antimicrobial peptide (AMP) development and identify 30 functional AMPs, of which six with broad-spectrum activity against drug-resistant pathogens.
- Amir Pandi
- , David Adam
- & Tobias J. Erb
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Article
| Open AccessPathogenesis-adaptive polydopamine nanosystem for sequential therapy of ischemic stroke
Reperfusion is a main strategy for restoring blood supply after ischemic stroke, but it induces neuroinflammation that undergoes dynamic progression, hindering the treatment of ischemic stroke. Here, the authors report a pathogenesis-adaptive nanosystem for sequential and on-demand regulation of reperfusion-induced dynamic neuroinflammation for ischemic stroke therapy.
- Di Wu
- , Jing Zhou
- & Zhong Chen
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Article
| Open AccessBioinspired porous three-coordinated single-atom Fe nanozyme with oxidase-like activity for tumor visual identification via glutathione
It is needed yet difficult to achieve a strategy for synthesizing single-atom nanozymes that integrate atomic metal dispersion, elevated mass transport and tailorable coordination environment. Here, the authors address this issue by developing a biomimetic synthetic strategy and demonstrate the application of the resultant single-atom Fe nanozymes for tumor visual identification.
- Da Chen
- , Zhaoming Xia
- & Yongquan Qu
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Article
| Open AccessA TRIM21-based bioPROTAC highlights the therapeutic benefit of HuR degradation
Overexpression of human antigen R (HuR) correlates with high grade tumours and poor patient prognosis. Here, the authors engineer a TRIM21 biological PROTAC to demonstrate the benefit of a targeted protein degradation approach to deplete HuR, resulting in tumour growth inhibition in pre-clinical cancer models by altering the HuR-regulated proteome.
- Alice Fletcher
- , Dean Clift
- & James Hunt
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Article
| Open AccessDeciphering triterpenoid saponin biosynthesis by leveraging transcriptome response to methyl jasmonate elicitation in Saponaria vaccaria
Methyl jasmonate triggers saponin production in Saponaria vaccaria. Using transcriptome data and heterologous expression, the authors identify P450s and glycosyltransferases that modify triterpenoids. They also discover the pathway for UDP-D-fucose biosynthesis.
- Xiaoyue Chen
- , Graham A. Hudson
- & Henrik V. Scheller
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Article
| Open AccessRational design of a JAK1-selective siRNA inhibitor for the modulation of autoimmunity in the skin
Therapeutic modulation of Janus kinase family enzymes is an established approach for inflammatory and autoimmune skin diseases. Here the authors rationally design small interfering RNAs to enable single Janus kinase targeting and test this new therapeutic approach in a skin disease model for maintaining efficacy and improving selectivity.
- Qi Tang
- , Hassan H. Fakih
- & John E. Harris
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Article
| Open AccessGreater wax moth control in apiaries can be improved by combining Bacillus thuringiensis and entrapments
The greater wax moth (GWM) is a major bee pest. Here, the authors show how a pest control method that combines a strain of Bacillus thuringiensis and a lure-based entrapment can help to control GWM using lab experiments and field beehives.
- Bo Han
- , Li Zhang
- & Pingli Dai
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Article
| Open AccessDissecting the human leptomeninges at single-cell resolution
The meninges protect the central nervous system at the brain border, and its dysfunction can lead to neural inflammation and cell damage. Here, the authors uncover the gene signatures of diverse cell types in the aged human leptomeninges and highlight their changes in Alzheimer’s Disease.
- Nicola A. Kearns
- , Artemis Iatrou
- & Yanling Wang
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Perspective
| Open AccessThe potential of CO2-based production cycles in biotechnology to fight the climate crisis
The utilization of one-carbon assimilation pathways for bioproduction represents a promising direction towards a more sustainable bio-based economy. Here, the authors compare the thermodynamic efficiencies and energy demand of C1-assimilation pathways and discuss their implementation for energy, material, and food production.
- Simone Bachleitner
- , Özge Ata
- & Diethard Mattanovich
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Article
| Open AccessCharge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism
Polymers are promising for mRNA delivery, but can have limited efficacy in hard to transfect cells. Here, the authors report charge-altering releasable transporters for improved mRNA transfection in primary T-lymphocytes and enhanced and selective protein expression in vivo.
- Zhijian Li
- , Laura Amaya
- & Paul A. Wender
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Article
| Open AccessRemodeling the cellular stress response for enhanced genetic code expansion in mammalian cells
Genetic code expansion (GCE) is a protein engineering tool that enables programmed and site-specific installation of noncanonical amino acids into proteins. Here, authors show that cellular stress remodelling boosts GCE in mammalian cells including GCE realized by orthogonally translating organelles.
- Mikhail E. Sushkin
- , Christine Koehler
- & Edward A. Lemke
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Article
| Open AccessAn in situ dual-anchoring strategy for enhanced immobilization of PD-L1 to treat autoimmune diseases
Immune checkpoints are critical in maintaining self-tolerance and their therapeutic modulation can be achieved in autoimmune diseases. Here the authors present an in situ dual-anchoring approach that targets PD-L1 and show effects in animal models of autoimmunity.
- Shenqiang Wang
- , Ying Zhang
- & Jicheng Yu
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Article
| Open AccessSelf-promoted electroactive biomimetic mineralized scaffolds for bacteria-infected bone regeneration
Infected bone defects are a major challenge in orthopedic treatment. Here, the authors develop an electroactive mineralized scaffold that achieves nearly complete in situ healing of infected bone in rats, rabbits and beagle dogs.
- Zixin Li
- , Danqing He
- & Yan Liu
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Article
| Open AccessAn autocatalytic multicomponent DNAzyme nanomachine for tumor-specific photothermal therapy sensitization in pancreatic cancer
Despite delivering gene-specific silencing, the use of deoxyribozymes (DNAzymes) for cancer therapy is limited by toxicity due to off-target effects. Here, the authors develop a multi-component DNAzyme, targeting both miRNA21 and HSP70, to induce tumour-specific sensitisation to photothermal therapy in preclinical models of pancreatic cancer.
- Jiaqi Yan
- , Xiaodong Ma
- & Hongbo Zhang
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Article
| Open AccessLactate biosensors for spectrally and spatially multiplexed fluorescence imaging
l-Lactate is increasingly recognized as a key metabolite and signalling molecule in mammals, but the methods to investigate it in vivo have been limited. Here, authors report a pair of improved biosensors—one green and one red—for visualizing l-lactate both inside and outside of cells.
- Yusuke Nasu
- , Abhi Aggarwal
- & Robert E. Campbell
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Article
| Open AccessRedox signaling-driven modulation of microbial biosynthesis and biocatalysis
Microbial communication has significant implications for industrial applications, but constructing communication systems which support coordinated behaviors is challenging. Here, the authors report an electron transfer triggered redox communication network and demonstrate its ability to coordinate microbial metabolism.
- Na Chen
- , Na Du
- & Quan Yuan
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Article
| Open AccessRNA-based translation activators for targeted gene upregulation
Many diseases are driven by the insufficient expression of critical genes, but few technologies are capable of rescuing these endogenous protein levels. Here, Cao et al. present an RNA-based technology that boosts protein production from endogenous mRNAs by upregulating their translation.
- Yang Cao
- , Huachun Liu
- & Bryan C. Dickinson
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Article
| Open AccessEnzymatic synthesis and nanopore sequencing of 12-letter supernumerary DNA
Unnatural base pairing xenonucleic acids (XNAs) can be used to expand life’s alphabet beyond ATGC. Here, authors show strategies for enzymatic synthesis and next-generation nanopore sequencing of XNA base pairs for reading and writing 12-letter DNA (ATGCBSPZXKJV).
- Hinako Kawabe
- , Christopher A. Thomas
- & Jorge A. Marchand
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Article
| Open AccessHidden prevalence of deletion-inversion bi-alleles in CRISPR-mediated deletions of tandemly arrayed genes in plants
The multiplex CRISPR system is the tool of choice for creating targeted tandemly arrayed genes (TAGs) deletions in plants. Here, the authors show that up to 80% of CRISPR-mediated TAG knockout alleles in Arabidopsis and rice are deletion-inversion bi-alleles, an unwanted products of targeted TAG deletions.
- Jiuer Liu
- , Feng-Zhu Wang
- & Jian-Feng Li
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Article
| Open AccessVisualization of accessible cholesterol using a GRAM domain-based biosensor
Regulated cholesterol transport is essential for the maintenance of cellular cholesterol distribution and homeostasis, but tools to monitor this process are limited. Here, the authors develop a genetically encoded cholesterol biosensor and demonstrate its use for visualising cellular cholesterol distribution in various live cells in real time.
- Dylan Hong Zheng Koh
- , Tomoki Naito
- & Yasunori Saheki
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Article
| Open AccessProlonged hydrogen production by engineered green algae photovoltaic power stations
Cost, scalability, and durability are critical factors determining the application of artificial photosynthesis systems. Here, the authors address these problems by inserting a carbon nanofiber into the chloroplast of green algae to transfer of electrons for photosynthesis and demonstrate H2 production up to 50 days.
- Hyo Jin Gwon
- , Geonwoo Park
- & Hyun S. Ahn
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Article
| Open AccessAn interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models
Here, the authors report the generation of a live but defective SARS-CoV-2 virus that is envelope-deficient and expresses human interferon beta. They show that nasal vaccination enhances mucosal and lung T cell response and provides pan-sarbecovirus protection in small animals.
- Chun-Kit Yuen
- , Wan-Man Wong
- & Kin-Hang Kok
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Article
| Open AccessDual targeted extracellular vesicles regulate oncogenic genes in advanced pancreatic cancer
KRASG12D mutations frequently co-occur with mutated TP53 tumour suppressor in patients with pancreatic ductal adenocarcinoma (PDAC). Here the authors report the design of dual targeted therapeutic extracellular vesicles containing high copy numbers of TP53 mRNA and siKRASG12D, showing anti-tumor activity in PDAC preclinical models.
- Chi-Ling Chiang
- , Yifan Ma
- & L. James Lee
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Article
| Open AccessMass production of lumenogenic human embryoid bodies and functional cardiospheres using in-air-generated microcapsules
Current methods to generate spheroids are associated with low production throughputs, limiting clinical and industrial translation. Here the authors present a clean ultra-high-throughput in-air microfluidic platform for mass production of lumenogenic embryoid bodies and functional cardiospheres.
- Bas van Loo
- , Simone A. ten Den
- & Jeroen Leijten
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Perspective
| Open AccessSynergistic investigation of natural and synthetic C1-trophic microorganisms to foster a circular carbon economy
Using one carbon (C1) molecules as primary feedstock for bioproduction holds great potential for a circular and carbon neutral economy. Here, the authors discuss the potential of merging knowledge gained from natural and synthetic C1-trophic organisms to expedite the development of efficient C1-based biomanufacturing.
- Enrico Orsi
- , Pablo Ivan Nikel
- & Stefano Donati
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Article
| Open AccessRepurposing conformational changes in ANL superfamily enzymes to rapidly generate biosensors for organic and amino acids
Biosensors have a wide number of potential applications, but rapidly constructing genetically encoded biosensors remains challenging. Here, authors report a method for rapidly converting ANL superfamily enzymes into biosensors for organic acids, based on their conformational changes upon binding.
- Jin Wang
- , Ning Xue
- & Meng Wang
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Article
| Open AccessCircular single-stranded DNA as switchable vector for gene expression in mammalian cells
Synthetic gene networks in mammalian cells are currently limited to either transcription factors or RNA regulators. Here, the authors develop a regulatory approach based on circular single-stranded DNA, which can be used as a conformationally switchable genetic vector in mammalian cells.
- Linlin Tang
- , Zhijin Tian
- & Jie Song
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Article
| Open AccessNanomechanical action opens endo-lysosomal compartments
Endo-lysosomal escape is a highly inefficient process. Here the authors present a lipid-based nanoscale molecular machine that achieves efficient cytosolic transport of biologics by destabilizing endo-lysosomal compartments through nanomechanical action upon light irradiation.
- Yu Zhao
- , Zhongfeng Ye
- & Qiaobing Xu
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Article
| Open AccessAromatized liposomes for sustained drug delivery
The development of liposome-based drug delivery systems has been hindered by the systemic toxicity and limited duration of effect due to insufficient drug loading and leakage of payload. Here the authors address these issues by designing aromatized liposomes that feature increased drug loading and slowed release compared to conventional liposomes.
- Yang Li
- , Tianjiao Ji
- & Daniel S. Kohane
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Article
| Open AccessAdaptive design of mRNA-loaded extracellular vesicles for targeted immunotherapy of cancer
There is an emerging interest in the use of mRNA therapeutics in cancer treatment, but their precise in vivo delivery remains a challenge. Here the authors develop IFN-γ mRNA-loaded small extracellular vesicles (sEVs) with CD64 overexpressed on their surface and demonstrate its efficacy in glioblastoma mouse models resistant to immunotherapy.
- Shiyan Dong
- , Xuan Liu
- & Wen Jiang
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Article
| Open AccessBiosynthesis and engineering of the nonribosomal peptides with a C-terminal putrescine
Nonribosomal peptides have diverse bioactivities and can possess unusual moieties at their C-terminus, such as polyamines. In this study, the authors identify a class of dodecapeptides glidonins that feature diverse N-terminal modifications and a uniform putrescine moiety at the C-terminus, elucidate their biosynthesis, and introduce the putrescine into the C-terminus of other nonribosomal peptides.
- Hanna Chen
- , Lin Zhong
- & Xiaoying Bian
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Article
| Open AccessmRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy
Large genes require dual adeno-associated viral (AAV) vectors for in vivo delivery/expression, but current methods have limitations. Here the authors develop and functionally evaluate REVeRT, an efficient and flexible dual AAV vector technology based on reconstitution via mRNA trans-splicing.
- Lisa Maria Riedmayr
- , Klara Sonnie Hinrichsmeyer
- & Elvir Becirovic
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Article
| Open AccessSonogenetic control of multiplexed genome regulation and base editing
Exogenous control of genes in vivo is important. Here the authors report a system that can be inducibly activated through thermal energy produced by ultrasound absorption and use this to control induction of gene activation and base editing: they apply this in cell lines and in a mouse model.
- Pei Liu
- , Josquin Foiret
- & Lei S. Qi
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Article
| Open AccessNIR-dye bridged human serum albumin reassemblies for effective photothermal therapy of tumor
Human serum albumin (HSA) can be used as a drug delivery material for cancer therapy. Here, the authors report an HSA-based photothermal platform that improves drug loading and photothermal therapeutic performance in breast cancer mouse models.
- Zhaoqing Shi
- , Miaomiao Luo
- & Hongzhong Chen
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