Featured
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Article
| Open AccessRepresentation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models
Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.
- Robert E. Hynds
- , Ariana Huebner
- & Charles Swanton
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Article
| Open AccessCircular single-stranded DNA as a programmable vector for gene regulation in cell-free protein expression systems
Protein expression vectors in cell-free systems mainly rely on double-stranded DNA and single-stranded RNA. Here, authors use circular single-stranded DNA as a programmable vector for gene regulation in a cell-free expression system by identifying its expression pathways.
- Zhijin Tian
- , Dandan Shao
- & Jie Song
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Article
| Open AccessIn-situ observation of silk nanofibril assembly via graphene plasmonic infrared sensor
Here, the authors develop a graphene plasmonic infrared sensor to probe the secondary structure of nanoscale assembly intermediates and the morphological evolution of silk nanofibrils, the fundamental building blocks of silk fibres.
- Chenchen Wu
- , Yu Duan
- & Qing Dai
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Article
| Open AccessTwo noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections
There are limited therapeutics available for treatment of mpox. In this study, the authors identify two non-competing human neutralizing monoclonal antibodies with protective effects against orthopoxvirus infection in a mouse model and structurally resolve the targeted epitope within the MPXV B6 protein.
- Runchu Zhao
- , Lili Wu
- & Qihui Wang
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Article
| Open AccessNanoscale cellular organization of viral RNA and proteins in SARS-CoV-2 replication organelles
The precise cellular localization of the SARS-CoV-2 RNA and replication partners has been elusive. Here, the authors use super-resolution fluorescence microscopy and specific labeling to reveal the nanoscale structure of viral replication organelles.
- Leonid Andronov
- , Mengting Han
- & W. E. Moerner
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Perspective
| Open AccessThe link between ancient microbial fluoride resistance mechanisms and bioengineering organofluorine degradation or synthesis
Microbial degradation and biosynthesis of fluorinated compounds is a field of increasing importance, but is hampered by the significant toxicity of fluoride. Here authors discuss emerging ideas on microbial defluorination/fluorination and fluoride resistance mechanisms, providing guidance on how this knowledge can guide future bioengineering approaches.
- Randy B. Stockbridge
- & Lawrence P. Wackett
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Article
| Open AccessGene expression signatures in blood from a West African sepsis cohort define host response phenotypes
Sepsis is a global challenge and a significant burden in Sub-Saharan Africa. Here, Chenoweth et al profile host gene expression signatures from a cohort in Ghana to define molecular phenotypes and identify potential targets to improve patient outcomes.
- Josh G. Chenoweth
- , Carlo Colantuoni
- & Danielle V. Clark
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Article
| Open AccessHigh-speed optical imaging with sCMOS pixel reassignment
The authors introduce a highspeed acquisition technique, sHAPR, for rapid exploration of biodynamics using fluorescence microscopy. The method leverages sCMOS cameras and custom fibre optics to convert microscopy images into 1D recordings, enabling acquisition at the maximum camera readout rate.
- Biagio Mandracchia
- , Corey Zheng
- & Shu Jia
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Article
| Open AccessMucus production, host-microbiome interactions, hormone sensitivity, and innate immune responses modeled in human cervix chips
Human cervical mucosa and its interactions with the microbiome play a central role in female reproductive tract health and disease. Here, the authors develop physiological models of the human cervix using Organ-on-a-Chip technology that produce mucus, and respond to hormonal, environmental, and microbial cues similar to the living cervix.
- Zohreh Izadifar
- , Justin Cotton
- & Donald E. Ingber
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Article
| Open AccessGermline Cas9 promoters with improved performance for homing gene drive
High-performance promoters are needed for gene drives; these are currently lacking in Drosophila melanogaster. Here the authors tested eleven Drosophila melanogaster germline promoters in several configurations and show higher drive conversion efficiency with minimal embryo resistance.
- Jie Du
- , Weizhe Chen
- & Jackson Champer
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Article
| Open AccessTemporal interference stimulation disrupts spike timing in the primate brain
Whether and how temporal interference (TI) stimulation disrupt primate oscillatory brain activity are not fully understood. Here authors show TI stimulation can non-invasively disrupt oscillatory brain activity but three factors make it too weak to impose new rhythms on the primate brain. Thus, it may be a potential method for safely controlling pathological brain activity.
- Pedro G. Vieira
- , Matthew R. Krause
- & Christopher C. Pack
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Article
| Open AccessA spatially localized DNA linear classifier for cancer diagnosis
Molecular computing is an emerging paradigm with a crucial role in clinical diagnosis. Here, authors develop a spatially localized, DNA-integrated circuits-based classifier, DNA IC-CLA, which enables accurate cancer diagnosis for clinical samples in a faster and more effective manner.
- Linlin Yang
- , Qian Tang
- & Da Han
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Article
| Open AccessNucleosomal DNA has topological memory
Here, the authors develop Topo-seq to measure the DNA topology (∆Lk) restrained by individual nucleosomes in vivo. They show that nucleosome DNA topology is imprinted by its native chromatin context and persists when the nucleosome is relocated.
- Joana Segura
- , Ofelia Díaz-Ingelmo
- & Joaquim Roca
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Article
| Open AccessControl of artificial membrane fusion in physiological ionic solutions beyond the limits of electroformation
Membrane fusion is crucial for fabricating artificial membranes. Here, the authors present an approach combining electric field with hydraulic pressure to physically control the fusion, enabling tuning of the shape and size of the 3D freestanding lipid bilayers in physiological solutions.
- Bong Kyu Kim
- , Dong-Hyun Kang
- & Tae Song Kim
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Article
| Open AccessLiquid foam improves potency and safety of gene therapy vectors
Gene therapy is a rapidly growing field, but is hindered by efficacy and safety concerns, including those related to delivery methods. Here, inspired by the use of foam in the delivery of pharmaceuticals, Dr. Stephan and colleagues formulated foam as a safe and effective delivery platform for gene therapy.
- K. Fitzgerald
- , S. B. Stephan
- & M. T. Stephan
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Article
| Open AccessPixel-wise programmability enables dynamic high-SNR cameras for high-speed microscopy
The researchers present an image sensor that allows every pixel to have independent exposure. It can sample a cell ROI’s fast fluorescence activity with long exposures at different phases, enhancing SNR and temporal resolution for capturing high-speed events.
- Jie Zhang
- , Jonathan Newman
- & Matthew Wilson
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Article
| Open AccessDynamic movement of the Golgi unit and its glycosylation enzyme zones
The structure of the Golgi and the localization of glycosylation enzymes remain largely elusive. Here, the authors use super-resolution microscopy to show that the Golgi is composed of small dynamic units which have rapidly moving zones of glycosylation enzymes.
- Akihiro Harada
- , Masataka Kunii
- & Akihiko Nakano
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Article
| Open AccessDeciphering bat influenza H18N11 infection dynamics in male Jamaican fruit bats on a single-cell level
Here, Kessler et al use single-cell RNA sequencing of the intestine and mesentery from H18N11 influenza-infected bats to show that viral infection is predominant in leukocytes and causes activation of immune cells and antiviral gene signatures.
- Susanne Kessler
- , Bradly Burke
- & Kevin Ciminski
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Article
| Open AccessA conserved Pol II elongator SPT6L mediates Pol V transcription to regulate RNA-directed DNA methylation in Arabidopsis
How to facilitate the transcription of plant-specific RNA Pol V is largely unknown. Liu et al. find that a conserved RNA Pol II elongator, SPT6L, mediates DNA methylation by its association with Pol V and promoting the production of scaffold RNA.
- Yujuan Liu
- , Jie Shu
- & Chen Chen
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Article
| Open AccessA variational expectation-maximization framework for balanced multi-scale learning of protein and drug interactions
Multi-scale learning still struggles with imbalanced information and greedy characteristics. Here the authors present MUSE, an Expectation-Maximization-based multi-scale framework, improving predictions across molecular interactions and atomic interfaces.
- Jiahua Rao
- , Jiancong Xie
- & Yuedong Yang
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Article
| Open AccessBiochemical-free enrichment or depletion of RNA classes in real-time during direct RNA sequencing with RISER
It is difficult to detect low abundance RNAs in sequencing experiments, and biochemical methods to enrich or deplete specific RNAs are time-consuming, costly and can damage RNA. Here, authors develop a biochemical-free technology to enrich or deplete RNA classes in real-time during direct RNA sequencing.
- Alexandra Sneddon
- , Agin Ravindran
- & Eduardo Eyras
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Article
| Open AccessSingle molecule delivery into living cells
Controlled manipulation of cultured cells by delivery of exogenous macromolecules is a cornerstone of experimental biology. Here, the authors describe a platform to deliver defined numbers of macromolecules into cultured cell lines at single molecule resolution.
- Chalmers C. Chau
- , Christopher M. Maffeo
- & Paolo Actis
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Article
| Open AccessIn-depth organic mass cytometry reveals differential contents of 3-hydroxybutanoic acid at the single-cell level
Comprehensive single-cell metabolic profiling is critical for revealing phenotypic heterogeneity and elucidating the molecular mechanisms underlying biological processes. Here, the authors establish a novel single-cell metabolomics platform for in-depth organic mass cytometry.
- Shaojie Qin
- , Yi Zhang
- & Yu Bai
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Article
| Open AccessImpact of secretin receptor homo-dimerization on natural ligand binding
GPCRs can form functionally important dimers. Here, authors study impact of dimerization of the secretin receptor on peptide ligand binding and show high receptor conformational dynamics that facilitate G protein recruitment and activation.
- Kaleeckal G. Harikumar
- , Sarah J. Piper
- & Laurence J. Miller
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Article
| Open AccessAngle between DNA linker and nucleosome core particle regulates array compaction revealed by individual-particle cryo-electron tomography
Here, using cryo-ET, the 3D structures of individual nucleosome particles were characterized to observe changes under varying ionic strengths and in the presence of protein H1, revealing key regulatory roles in chromatin organization dynamics.
- Meng Zhang
- , César Díaz-Celis
- & Gang Ren
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Article
| Open AccessDevelopment of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus
Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating widely in birds and have recently caused large outbreaks in mammals. Here, Furey et al. develop a clade 2.3.4.4b HA-expressing mRNA-LNP vaccine and show that it elicits strong protective immune responses in mice and ferrets.
- Colleen Furey
- , Gabrielle Scher
- & Scott E. Hensley
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Article
| Open AccessSolutes unmask differences in clustering versus phase separation of FET proteins
Biomolecular condensates form via phase separation of multivalent macromolecules. Phase separation is governed by solubility whereas multivalence drives percolation, also known as gelation. The authors in this work identify the distinct energy and length scales that influence phase separation versus percolation.
- Mrityunjoy Kar
- , Laura T. Vogel
- & Rohit V. Pappu
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Article
| Open AccessCystine-knot peptide inhibitors of HTRA1 bind to a cryptic pocket within the active site region
Here the authors use phage display to develop cystine-knot peptides that inhibit the trimeric serine protease HTRA1. Structural and biochemical characterisation uncovered binding of the peptides to a cryptic pocket that locked the active site in a noncompetent state.
- Yanjie Li
- , Yuehua Wei
- & Daniel Kirchhofer
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Article
| Open AccessIntegrating cryo-OrbiSIMS with computational modelling and metadynamics simulations enhances RNA structure prediction at atomic resolution
Conventional structural biology techniques are limited in deciphering complex RNA structures and dynamic interactions. Here the authors show an integrated approach that combines cryogenic OrbiSIMS (cryo-OrbiSIMS) with computational methods for modelling RNA structures at atomic resolution.
- Shannon Ward
- , Alex Childs
- & Aditi N. Borkar
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Article
| Open AccessActive transcription and epigenetic reactions synergistically regulate meso-scale genomic organization
Chromatin within interphase nuclei forms compacted nanoscale DNA domains of uniform size. By integrating theory and imaging, here the authors show how the interplay between transcription and epigenetic mechanisms determine this size, independent of cell type.
- Aayush Kant
- , Zixian Guo
- & Vivek B. Shenoy
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Article
| Open AccessCellular structure of dinosaur scales reveals retention of reptile-type skin during the evolutionary transition to feathers
The evolution of feathers is associated with the evolution of related skin microstructures. Here, the authors demonstrate that Psittacosaurus, a non-avian feathered dinosaur, retained scaled skin like its ancestors in body regions lacking feathers.
- Zixiao Yang
- , Baoyu Jiang
- & Maria E. McNamara
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Article
| Open AccessThe actin cytoskeleton plays multiple roles in structural colour formation in butterfly wing scales
NCOMMS-23-44446C Vivid structural colours in butterflies are caused by photonic nanostructures scattering light, however insight into the development of such structures in vivo remains scarce. Here the authors show that actin plays a vital and direct templating role during structural colour formation in butterfly scales, providing ridge patterning mechanisms that are likely universal across lepidoptera.
- Victoria J. Lloyd
- , Stephanie L. Burg
- & Andrew J. Parnell
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Article
| Open AccessCopper(I)-nitrene platform for chemoproteomic profiling of methionine
Methionine plays an essential role in various biological and cell regulatory processes, making its chemoproteomic profiling necessary to understand its function. Here, the authors present Copper(I)-Nitrene Platform (CuNiP) for robust and selective labelling of methionine to generate highly stable sulfonyl sulfimide conjugates under physiological conditions.
- Samrat Sahu
- , Benjamin Emenike
- & Monika Raj
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Article
| Open AccessInvariant γδTCR natural killer-like effector T cells in the naked mole-rat
Naked mole-rats are long-lived rodents known to be resistant to the development of cancer, yet their immune system remains poorly explored. Here, the authors identify natural killer-like effector γδ T cells that express a dominant γδ T cell receptor and may serve a role in tumour immunosurveillance.
- Guillem Sanchez Sanchez
- , Stephan Emmrich
- & David Vermijlen
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Article
| Open AccessPhotoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN) for cross-modal individual analysis of the whole brain
Here, the authors introduce Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN) - a high-speed, non-destructive photoacoustic brain imaging technique that constructs 3D fluorescent maps of the brain and improves upon some of the limitations associated with traditional whole-brain optical imaging techniques.
- Yuwen Chen
- , Haoyu Yang
- & Bo Lei
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Article
| Open AccessLong-term relapse-free survival enabled by integrating targeted antibacteria in antitumor treatment
Tumor-resident intracellular microbiota (TRIM) could be a potential target for anticancer treatment. Here the authors report Au@Ag2Se nano-assemblies enabling bacterial killing, tumor inhibition and immune regulation in tumor microenvironment.
- Yuanlin Wang
- , Yaqian Han
- & Miao Yu
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Article
| Open AccessThe matrisome landscape controlling in vivo germ cell fates
The developmental fate of cells is regulated by the delicate environment created by the extracellular matrix. Here, authors investigate the impact of the full complement of conserved matrisome genes in germ cell development and gamete health in C. elegans.
- Aqilah Amran
- , Lara Pigatto
- & Sandeep Gopal
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Article
| Open AccessBioinformatics leading to conveniently accessible, helix enforcing, bicyclic ASX motif mimics (BAMMs)
Researchers mimic protein interface helices by stapling peptide side chains, or replacing hydrogen bonds with covalent ones, and synthetic helical mimics are heavily biased towards stapling. Here the authors describe bioinformatic discovery of hydrophobic triangles at helix N-termini, and rigid, bicyclic synthetic mimics of them.
- Tianxiong Mi
- , Duyen Nguyen
- & Kevin Burgess
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Article
| Open AccessHigh-throughput mechanical phenotyping and transcriptomics of single cells
The molecular system regulating cell surface mechanics remains largely unexplored at single-cell resolution. Here, the authors report a high-throughput single-cell assay, ELASTomics, which integrates mechanical phenotyping with unbiased transcriptomics.
- Akifumi Shiomi
- , Taikopaul Kaneko
- & Hirofumi Shintaku
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Article
| Open AccessStructural mechanisms for binding and activation of a contact-quenched fluorophore by RhoBAST
FLAPs have recently emerged as RNA counterparts to fluorescent proteins. Here, the authors determine the crystal structure of a FLAP called RhoBAST in complex with its ligand TMR-DN and reveal the mechanisms for binding and activation.
- Yufan Zhang
- , Zhonghe Xu
- & Xianyang Fang
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Article
| Open AccessZero-shot learning enables instant denoising and super-resolution in optical fluorescence microscopy
The authors introduce ZS-DeconvNet, an unsupervised computational super-resolution method for multiple types of microscopes, that enhances image resolution by more than 1.5 times over the diffraction limit with 10 times lower fluorescence than regular superresolution imaging conditions.
- Chang Qiao
- , Yunmin Zeng
- & Qionghai Dai
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Article
| Open AccessCorrelative single molecule lattice light sheet imaging reveals the dynamic relationship between nucleosomes and the local chromatin environment
This study combines lattice light sheet microscopy and single molecule imaging to study protein dynamics and chromatin structure in live cells. The authors describe how nucleosomes and proteins move and are organised in relation to chromatin density.
- Timothy A. Daugird
- , Yu Shi
- & Wesley R. Legant
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Article
| Open AccessMolecular fingerprinting of biological nanoparticles with a label-free optofluidic platform
Biosensing tools to detect multiple analytes in a high-throughput manner are still hindered by many limitations. Here, the authors present a label-free optofluidic platform integrating digital holography and microfluidics for analyte detection, allowing for the fingerprinting of heterogenous biological samples.
- Alexia Stollmann
- , Jose Garcia-Guirado
- & Romain Quidant
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Article
| Open AccessHepatocytes differentiate into intestinal epithelial cells through a hybrid epithelial/mesenchymal cell state in culture
Hepatocytes dedifferentiate into progenitor-like cells in culture. Here, authors elucidate the dynamics and mechanisms of hepatocyte dedifferentiation and find an unexpected differentiation potential of hepatocytes into intestinal epithelial cells.
- Shizuka Miura
- , Kenichi Horisawa
- & Atsushi Suzuki
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Article
| Open AccessEnzyme-assisted high throughput sequencing of an expanded genetic alphabet at single base resolution
The expansion of the genetic code with synthetic nucleotides has broadened our ability to evolve DNA as a functional material, but we lack analytical tools for the expanded alphabet. Here the authors demonstrate an enzyme-assisted method for the sequencing of six-letter DNA.
- Bang Wang
- , Kevin M. Bradley
- & Steven A. Benner
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Article
| Open AccessDynamin1 long- and short-tail isoforms exploit distinct recruitment and spatial patterns to form endocytic nanoclusters
Dynamins are required at nascent endosomes to promote membrane fission. Here, the authors use super-resolution microscopy to show that dynamin-1 recruitment relies on pre-existing nanoclusters and trapping of molecules laterally diffusing on the plasma membrane.
- Anmin Jiang
- , Kye Kudo
- & Frédéric A. Meunier
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Article
| Open AccessProteome partitioning constraints in long-term laboratory evolution
Adaptive laboratory evolution provides a real-time record of physiological change. In bacteria adapted to glucose over 40 000 generations, this study finds an apparent increase in enzyme efficiency consistent with increased substrate saturation due to loss of a flux sensing mechanism early in adaptation.
- Matteo Mori
- , Vadim Patsalo
- & Matthew Scott
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Article
| Open AccessThree-dimensional liquid metal-based neuro-interfaces for human hippocampal organoids
Providing a suitable multi-electrode array (MEA) for free-floating neural organoids is a great challenge. Here, authors present a mesh soft stretchable MEA for recording neural signals in human hippocampal organoids derived from induced pluripotent stem cells.
- Yan Wu
- , Jinhao Cheng
- & Xingyu Jiang
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Article
| Open AccessGene editing for latent herpes simplex virus infection reduces viral load and shedding in vivo
The main challenge for anti-HSV therapy is to target latent virus in ganglionic neurons. Here, the authors report a well-tolerated anti-HSV gene editing approach against HSV which targets latent HSV genomes and leads to reductions of ganglionic viral loads, and viral shedding upon reactivation in mouse models.
- Martine Aubert
- , Anoria K. Haick
- & Keith R. Jerome
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