Biology subjects

Yang, Z.

Publications and source records attributed to Yang, Z..

At least 487 records · Page 27Linked to original sources

bioRxiv2021

A H3K9me2-Binding Protein AGDP3 Limits DNA Methylation and Transcriptional Gene Silencing in Arabidopsis

DNA methylation is critical for tuning gene expression to prevent potentially deleterious gene-silencing. The Arabidopsis DNA glycosylase/lyase REPRESSOR OF SILENCING 1 (ROS1) initiates active DNA demethylation and is required for the prevention of DNA hypermethylation at thousands of genomic loci. However, the mechanism recruiting ROS1 to specific loci is not well understood. Here, we report the discovery of Arabidopsis AGENET Domain Containing Protein 3 (AGDP3) as a cellular factor required for ROS1-mediated DNA demethylation, and targets ROS1 to specific loci. We found that AGDP3 could bind to the H3K9me2 mark by its AGD12 cassette. The crystal structure of the AGDP3 AGD12 in complex with an H3K9me2 peptide reveals the molecular basis for the specific recognition, that the dimethylated H3K9 and unmodified H3K4 are specifically anchored into two different surface pockets. Interestingly, a histidine residue located in the methylysine binding aromatic cage enables AGDP3 pH-dependent H3K9me2 binding capacity. Considering the intracellular pH correlates with the histone acetylation status, our results provide the molecular mechanism for the regulation of ROS1 DNA demethylase by the gene silencing H3K9me2 mark and the potential crosstalk with active histone acetylation mark.

plant biology↗

bioRxiv2021

Comprehensive Assessment of Somatic Copy Number Variation Calling Using Next-Generation Sequencing Data

Copy number variation (CNV) is a common type of mutation that often drives cancer progression. With advances in next-generation sequencing (NGS), CNVs can be detected in a detailed manner via newly developed computational tools but quality of such CNV calls has not been carefully evaluated. We analyzed CNV calls reported by 6 cutting-edge callers for 91 samples which were derived from the same cancer cell line, prepared and sequenced by varying the following factors: type of tissue sample (Fresh vs. Formalin Fixed Paraffin Embedded (FFPE)), library DNA amount, tumor purity, sequencing platform (Whole-Genome Sequencing (WGS) versus Whole-Exome Sequencing (WES)), and sequencing coverage. We found that callers greatly determined the pattern of CNV calls. Calling quality was drastically impaired by low purity (<50%) and became variable when WES, FFPE, and medium purity (50%-75%) were applied. Effects of low DNA amount and low coverage were relatively minor. Our analysis demonstrates the limitation of benchmarking somatic CNV callers when the real ground truth is not available. Our comprehensive analysis has further characterized each caller with respect to confounding factors and examined the consistency of CNV calls, thereby providing guidelines for conducting somatic CNV analysis.

bioinformatics↗

bioRxiv2021

Deep Learning-Based Approaches for Decoding Motor Intent from Peripheral Nerve Signals

The ultimate goal of an upper-limb neuroprosthesis is to achieve dexterous and intuitive control of individual fingers. Previous literature shows that deep learning (DL) is an effective tool to decode the motor intent from neural signals obtained from different parts of the nervous system. However, it still requires complicated deep neural networks that are inefficient and not feasible to work in real-time. Here we investigate different approaches to enhance the efficiency of the DL-based motor decoding paradigm. First, a comprehensive collection of feature extraction techniques is applied to reduce the input data dimensionality. Next, we investigate two different strategies for deploying DL models: a one-step (1S) approach when big input data are available and a two-step (2S) when input data are limited. With the 1S approach, a single regression stage predicts the trajectories of all fingers. With the 2S approach, a classification stage identifies the fingers in motion, followed by a regression stage that predicts those active digits trajectories. The addition of feature extraction substantially lowers the motor decoders complexity, making it feasible for translation to a real-time paradigm. The 1S approach using a recurrent neural network (RNN) generally gives better prediction results than all the ML algorithms with mean squared error (MSE) ranges from 10-3 to 10-4 for all finger while variance accounted for (VAF) scores are above 0.8 for the most degree of freedom (DOF). This result reaffirms that DL is more advantageous than classic ML methods for handling a large dataset. However, when training on a smaller input data set as in the 2S approach, ML techniques offers a simpler implementation while ensuring comparably good decoding outcome to the DL ones. In the classification step, either machine-learning (ML) or DL models achieve the accuracy and F1 score of 0.99. Thanks to the classification step, in the regression step, both types of models result in comparable MSE and VAF scores as those of the 1S approach. Our study outlines the trade-offs to inform the implementation of real-time, low-latency, and high accuracy DL-based motor decoder for clinical applications.

bioengineering↗

bioRxiv2021

SARS-CoV-2 lineage B.1.526 emerging in the New York region detected by software utility created to query the spike mutational landscape

Wide-scale SARS-CoV-2 genome sequencing is critical to tracking viral evolution during the ongoing pandemic. Variants first detected in the United Kingdom, South Africa, and Brazil have spread to multiple countries. We developed the software tool, Variant Database (VDB), for quickly examining the changing landscape of spike mutations. Using VDB, we detected an emerging lineage of SARS-CoV-2 in the New York region that shares mutations with previously reported variants. The most common sets of spike mutations in this lineage (now designated as B.1.526) are L5F, T95I, D253G, E484K or S477N, D614G, and A701V. This lineage was first sequenced in late November 2020 when it represented <1% of sequenced coronavirus genomes that were collected in New York City (NYC). By February 2021, genomes from this lineage accounted for ~32% of 3288 sequenced genomes from NYC specimens. Phylodynamic inference confirmed the rapid growth of the B.1.526 lineage in NYC, notably the sub-clade defined by the spike mutation E484K, which has outpaced the growth of other variants in NYC. Pseudovirus neutralization experiments demonstrated that B.1.526 spike mutations adversely affect the neutralization titer of convalescent and vaccinee plasma, indicating the public health importance of this lineage.

bioinformatics↗

bioRxiv2021

Complex introgression history of the erato-sara clade of Heliconius butterflies

AO_SCPLOWBSTRACTC_SCPLOWIntrogressive hybridization plays a key role in adaptive evolution and species diversification in many groups of species. However, frequent hybridization and gene flow between species makes estimation of the species phylogeny and key population parameters challenging. Here, we show that by accounting for phasing and using full-likelihood analysis methods, introgression histories and population parameters can be estimated reliably from whole-genome sequence data. We employ full-likelihood methods under the multispecies coalescent (MSC) model with and without gene flow to analyze the genomic data from six members of the erato-sara clade of Heliconius butterflies and infer the species phylogeny and cross-species introgression events. The methods naturally accommodate random fluctuations in genealogical history across the genome due to deep coalescence. To avoid heterozygote phasing errors in haploid sequences commonly produced by genome assembly methods, we process and compile unphased diploid sequence alignments and use analytical methods to average over uncertainties in heterozygote phase resolution. There is robust evidence for introgression across the genome, both among distantly related species deep in the phylogeny and between sister species in shallow parts of the tree. We obtain chromosome-specific estimates of key population parameters such as introgression directions, times and probabilities, as well as species divergence times and population sizes for modern and ancestral species. We confirm ancestral gene flow between the sara clade and an ancestral population of H. telesiphe, a likely hybrid speciation origin for H. hecalesia, and gene flow between sister species H. erato and H. himera. Inferred introgression among ancestral species also explains the history of two chromosomal inversions deep in the phylogeny of the group. This study illustrates how a full-likelihood approach based on the multispecies coalescent makes it possible to extract rich historical information of species divergence and gene flow from genomic data.

evolutionary biology↗

bioRxiv2021

CRISPR targeting of MEIOTIC-TOPOISOMERASE VIB-dCas9 to a recombination hotspot is insufficient to increase crossover frequency in Arabidopsis

During meiosis, homologous chromosomes pair and recombine, which can result in reciprocal crossovers that increase genetic diversity. Crossovers are unevenly distributed along eukaryote chromosomes and show repression in heterochromatin and the centromeres. Within the chromosome arms crossovers are often concentrated in hotspots, which are typically in the kilobase range. The uneven distribution of crossovers along chromosomes, together with their low number per meiosis, creates a limitation during crop breeding, where recombination can be beneficial. Therefore, targeting crossovers to specific genome locations has the potential to accelerate crop improvement. In plants, meiotic crossovers are initiated by DNA double strand breaks (DSBs) that are catalysed by SPO11 complexes, which consist of two catalytic (SPO11-1 and SPO11-2) and two non-catalytic subunits (MTOPVIB). We used the model plant Arabidopsis thaliana to target a dCas9-MTOPVIB fusion protein to the 3a crossover hotspot via CRISPR. We observed that this was insufficient to significantly change meiotic crossover frequency or pattern within 3a. We discuss the implications of our findings for targeting meiotic recombination within plant genomes.

plant biology↗

bioRxiv2021

Silencing of lncRNA NEAT1 inhibits esophageal squamous cell carcinoma proliferation, migration, and invasion via regulation of the miR-1299/MMP2 axis

Esophageal squamous cell carcinoma (ESCC) is the most prevalent form of esophageal cancer worldwide. Considerable evidence has verified that abnormal expression of lncRNAs can effectively influence the progression of various malignant tumors. However, the regulatory mechanisms of lncRNAs underlying ESCC development and progression remain poorly defined. Here, we investigated the role of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in ESCC via regulating microRNA 1299 (miR-1299) and matrix metalloproteinase 2 (MMP2). A total of 32 ESCC tissue samples were obtained from the First Affiliated Hospital of Zhengzhou University. The mRNA levels of lncRNA NEAT1, miR-1299, and MMP2 mRNA were measured via quantitative real-time PCR. Interactions among miR-1299, lncRNA NEAT1, and MMP2 mRNA in EC9706 cells were confirmed by dual-luciferase reporter assays and RNA immunoprecipitation (RIP) assays. The proliferation and migration/invasion of ESCC cells were verified by CCK-8 and transwell assays, respectively. lncRNA NEAT1 was up-regulated in ESCC tissues and cells. lncRNA NEAT1 silencing inhibited migration, invasion, and proliferation of ESCC cells. Furthermore, lncRNA NEAT1 sponged and negatively regulated miR-1299, thus giving rise to increased expression of MMP2. Moreover, miR-1299 inhibitors and MMP2 rescued the invasion of ESCC cells following silencing of lncRNA NEAT1. lncRNA NEAT1 was overexpressed in ESCC tissues and cells. Silencing of lncRNA NEAT1 inhibited ESCC proliferation, migration, and invasion via reducing competitive binding of lncRNA NEAT1 with miR-1299 and enhancing miR-1299-targeted suppression of MMP2. Taken together, our findings suggest that lncRNA NEAT1 is a potential target for ESCC therapy and rehabilitation.

cancer biology↗

bioRxiv2021

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease 2019 (COVID-19) including two novel mRNA-based vaccines1,2. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known3-6. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S) and receptor binding domain (RBD) binding titers3,5,6. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection7,8. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

immunology↗

bioRxiv2021

The hyperlipidaemic drug fenofibrate significantly reduces infection by SARS-CoV-2 in cell culture models

The SARS-CoV-2 pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure dimerization of ACE2, the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate. Fenofibric acid also destabilized the receptor binding domain (RBD) of the viral spike protein and inhibited RBD binding to ACE2 in ELISA and whole cell binding assays. Fenofibrate and fenofibric acid were tested by two independent laboratories measuring infection of cultured Vero cells using two different SARS-CoV-2 isolates. In both settings at drug concentrations which are clinically achievable, fenofibrate and fenofibric acid reduced viral infection by up to 70%. Together with its extensive history of clinical use and its relatively good safety profile, these studies identify fenofibrate as a potential therapeutic agent requiring urgent clinical evaluation to treat SARS-CoV-2 infection. TeaserThe approved drug fenofibrate inhibits infection by SARS-COV-2

pharmacology and toxicology↗

bioRxiv2020

Growth stage-dependent changes of the levels of keratin 1 and keratin 10 as well as the green autofluorescence of the skin of the back and the ears of C57BL/6 mice under basal conditions and after UVC irradiation

Our previous studies have indicated that oxidative stress and inflammation can dose-dependently induce increased skins green autofluorescence (AF) of mice, which results at least partially from keratin 1 (K1) cleavage. Increased green AF was also found in patients skin of several major diseases, which may become a novel biomarker for non-invasive diagnosis. We also found age-dependent changes of the skins green AF of natural populations. In this study we tested our hypothesis that there are growth stage-dependent changes of K1 and keratin 10 (K10) levels in the skin of mice, which may underlie the age-dependent changes of the skins green AF. We found that in the skin of both mices back and ears, there were growth stage-dependent changes of the levels of K1 and K10 as well as the basal green AF. The K1 and K10 levels in the backs skin were significantly different from those in the ears skin. There were also growth stage-dependent changes of the UVC-induced changes of K1 and K10 levels of both the ears and the back. Collectively, our study has provided first evidence showing growth stage-dependent and differential changes of the levels of K1 and K10 as well as skins green AF in the back and the ears of mice under basal conditions and after UVC irradiation. These findings are valuable for understanding the age-dependent changes of the skins green AF of natural populations, which are also important for establishing the keratins AF-based method for non-invasive diagnosis of diseases.

developmental biology↗

bioRxiv2020

In vivo genetic screen identifies a SLC5A3-dependent myo-inositol auxotrophy in acute myeloid leukemia

An enhanced requirement for extracellular nutrients is a hallmark property of cancer cells. Here, we optimized an in vivo genetic screening strategy for evaluating dependencies in acute myeloid leukemia (AML), which led to the identification of the myo-inositol transporter SLC5A3 as a unique vulnerability in this disease. In accord with this transport function, we demonstrate that the SLC5A3 dependency reflects a myo-inositol auxotrophy in AML. Importantly, the commonality among SLC5A3-dependent AML lines is the transcriptional silencing of ISYNA1, which encodes the rate limiting enzyme for myoinositol biosynthesis, inositol-3-phosphate synthase 1. We used gain- and loss-of-function experiments to demonstrate a synthetic lethal genetic interaction between ISYNA1 and SLC5A3 in AML, which function redundantly to sustain intracellular myo-inositol. Transcriptional silencing and DNA hypermethylation of ISYNA1 occur in a recurrent manner in human AML patient samples, in association with the presence of IDH1/IDH2 and CEBPA mutations. Collectively, our findings reveal myo-inositol auxotrophy as a novel form of metabolic dysregulation in AML, which is caused by the aberrant silencing of a biosynthetic enzyme. Statement of significanceHere, we show how epigenetic silencing can provoke a nutrient dependency in AML by exploiting a synthetic lethality relationship between biosynthesis and transport of myo-inositol. Blocking the function of this solute carrier may have therapeutic potential in an epigenetically-defined subset of AML.

cancer biology↗

bioRxiv2020

Autonomous sensing the insulin peptide by an olfactory G protein coupled receptor modulates glucose metabolism

Along with functionally intact insulin, diabetes-associated insulin peptides are secreted by {beta} cells(1-3). By screening the expression and functional characterization of olfactory receptors in pancreatic islets, we identified Olfr109 as the receptor to detect insulin peptides. Engagement of one insulin peptide, insB:9-23, with Olfr109 diminished insulin secretion through Gi-cAMP signalling and promoted macrophage proliferation. Remarkably, Olfr109 deficiency alleviated intra-islet inflammatory responses and improved glucose homeostasis in Akita- and HFD-fed mice. We further determined the binding mode between the insB:9-23 and Olfr109. A pepducin-based Olfr109 antagonist improved glucose homeostasis in diabetic and obese mouse models. Collectively, we found that pancreatic {beta} cells use Olfr109 to autonomously detect self-secreted insulin peptides and this detection arrests insulin secretion and crosstalk with macrophages to increase intra-islet inflammation.

physiology↗

bioRxiv2020

A midbrain - thalamus - cortex circuit reorganizes cortical dynamics to initiate planned movement

Motor behaviors are often planned long before execution, but only released after specific sensory events. Planning and execution are each associated with distinct patterns of motor cortex activity. Key questions are how these dynamic activity patterns are generated and how they relate to behavior. Here we investigate the multi-regional neural circuits that link an auditory go cue and the transition from planning to execution of directional licking. Ascending glutamatergic neurons in the midbrain reticular and pedunculopontine nuclei show short-latency and phasic changes in spike rate that are selective for the go cue. This signal is transmitted via the thalamus to the motor cortex, where it triggers a rapid reorganization of motor cortex state from planning-related activity to a motor command, which in turn drives appropriate movement. Our studies show how brainstem structures can control cortical dynamics via the thalamus for rapid and precise motor behavior.

neuroscience↗

bioRxiv2020

The SEQC2 Epigenomics Quality Control (EpiQC) Study: Comprehensive Characterization of Epigenetic Methods, Reproducibility, and Quantification

Cytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify cancer and other diseases. However, the wide variety of approaches available to interrogate these modifications has created a need for harmonized materials, methods, and rigorous benchmarking to improve genome-wide methylome sequencing applications in clinical and basic research. Here, we present a multi-platform assessment and a global resource for epigenetics research from the FDAs Epigenomics Quality Control (EpiQC) Group. The study design leverages seven human cell lines that are designated as reference materials and publicly available from the National Institute of Standards and Technology (NIST) and Genome in a Bottle (GIAB) consortium. These samples were subject to a variety of genome-wide methylation interrogation approaches across six independent laboratories, with a primary focus was on 5-methylcytosine modifications. Each sample was processed in two or more technical replicates by three whole-genome bisulfite sequencing (WGBS) protocols (TruSeq DNA methylation, Accel-NGS MethylSeq, and SPLAT), oxidative bisulfite sequencing (TrueMethyl), one enzymatic deamination method (EMseq), targeted methylation sequencing (Illumina Methyl Capture EPIC), and single-molecule long-read nanopore sequencing from Oxford Nanopore Technologies. After rigorous quality assessment and comparison to Illumina EPIC methylation microarrays and testing on a range of algorithms (Bismark, BitmapperBS, BWAMeth, and GemBS), we found overall high concordance between assays (R=0.87-R0.93), differences in efficency of read mapping and CpG capture and coverage, and platform performance. The data provided herein can guide continued used of these reference materials in epigenomics assays, as well as provide best practices for epigenomics research and experimental design in future studies.

genomics↗

bioRxiv2020

Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies

SARS-CoV-2 unprecedentedly threatens the public health at worldwide level. There is an urgent need to develop an effective vaccine within a highly accelerated time. Here, we present the most comprehensive S-protein-based linear B-cell epitope candidate list by combining epitopes predicted by eight widely-used immune-informatics methods with the epitopes curated from literature published between Feb 6, 2020 and July 10, 2020. We find four top prioritized linear B-cell epitopes in the hotspot regions of S protein can specifically bind with serum antibodies from horse, mouse, and monkey inoculated with different SARS-CoV-2 vaccine candidates or a patient recovering from COVID-19. The four linear B-cell epitopes can induce neutralizing antibodies against both pseudo and live SARS-CoV-2 virus in immunized wild-type BALB/c mice. This study suggests that the four linear B-cell epitopes are potentially important candidates for serological assay or vaccine development.

microbiology↗

bioRxiv2020

Distinct expression of select and transcriptome-wide isolated 3'UTRs suggests critical roles in development and transition states

Mature mRNA molecules are typically considered to be comprised of a 5UTR, a 3UTR and a coding region (CDS), all attached until degradation. Unexpectedly, however, there have been multiple recent reports of widespread differential expression of mRNA 3UTRs and their cognate coding regions, resulting in the expression of isolated 3UTRs (i3UTRs); these i3UTRs can be highly expressed, often in reciprocal patterns to their cognate CDS. Similar to the role of other lncRNAs, isolated 3UTRs are likely to play an important role in gene regulation but little is known about the contexts in which they are deployed. To begin to parse the functions of i3UTRs, here we carry out in vitro, in vivo and in silico analyses of differential 3UTR/CDS mRNA ratio usage across tissues, development and cell state changes both for a select list of developmentally important genes as well as through unbiased transcriptome-wide analyses. Across two developmental paradigms we find a distinct switch from high i3UTR expression of stem cell related genes in proliferating cells compared to newly differentiated cells. Our unbiased transcriptome analysis across multiple gene sets shows that regardless of tissue, genes with high 3UTR to CDS ratios belong predominantly to gene ontology categories related to cell-type specific functions while in contrast, the gene ontology categories of genes with low 3UTR to CDS ratios are similar and relate to common cellular functions. In addition to these specific findings our data provide critical information from which detailed hypotheses for individual i3UTRs can be tested-with a common theme that i3UTRs appear poised to regulate cell-specific gene expression and state. Significance StatementThe widespread existence and expression of mRNA 3 untranslated sequences in the absence of their cognate coding regions (called isolated 3UTRs or i3UTRs) opens up considerable avenues for gene regulation not previously envisioned. Each isolated 3UTR may still bind and interact with micro RNAs, RNA binding proteins as well as other nucleic acid sequences, all in the absence or low levels of cognate protein production. Here we document the expression, localization and regulation of i3UTRs both within particular biological systems as well as across the transcriptome. As this is an entirely new area of experimental investigation these early studies are seminal to this burgeoning field.

cell biology↗

bioRxiv2020

An uncanonical transcription factor-DREB2B regulates seed vigor negatively through ABA pathway

Seed vigor is an important trait for ecology, agronomy, and economy and varies with different plant species and environmental conditions. Dehydration-Responsive Element-Binding Protein 2B (DREB2B), a subgroup of the DREB transcription factor family, is well-known in drought resistance. However, the role of DREB2B in the regulation of seed vigor has not been identified. Here, we found that DREB2B is a negative regulator of seed vigor by ABA-mediated pathway in Arabidopsis with loss of function mutant and over-expressed transgenic lines. Furthermore, DREB2B showed epistatic and parallel to ABI3 simultaneously in seed vigor regulation by genetic and molecular approaches. DREB2B homolog gene (GhDREB2B-A09) was also identified in cotton. The expression analysis indicated that transcripts of DREB2B were higher in mature dry seed, and the transgenic plants showed the conservative roles of DREB2B in Arabidopsis and cotton. In addition, we identified that DREB2B interacted with RADICAL-INDUCED CELL DEATH1 (RCD1) to involve seed vigor regulation together in Arabidopsis and cotton with BiFC experiment and mutant phenotypic analysis. Collectively it is concluded that DREB2B interacting with RCD1 or SRO1 function at upstream of and synergistic with ABI3 to regulate seed vigor negatively in Arabidopsis and cotton, which provides novel knowledge in the seed development study. HighlightsDREB2B transcription is seed specific and a negative regulator of seed vigor by ABA-mediated pathway, which interacts with RCD1s, and functions synergistically with ABI3 to affecet seed germination and vigor in Arabidopsis and cotton.

plant biology↗

bioRxiv2020

Intranasal administration of SARS-CoV-2 neutralizing human antibody prevents infection in mice

Prevention of SARS-CoV-2 infection at the point of nasal entry is a novel strategy that has the potential to help contain the ongoing pandemic. Using our proprietary technologies, we have engineered a human antibody that recognizes SARS-CoV-2 S1 spike protein with an enhanced affinity for mucin to improve the antibodys retention in respiratory mucosa. The modified antibody, when administered into mouse nostrils, was shown to block infection in mice that were exposed to high titer SARS-CoV-2 pseudovirus 10 hours after the initial antibody treatment. Our data show that the protection against SARS-CoV-2 infection is effective in both nasal and lung areas 7 days after viral exposure. The modified antibody is stable in a nasal spray formulation and maintains its SARS-CoV-2 neutralizing activity. Nasal spray of the modified antibody can be developed as an affordable and effective prophylactic product to protect people from infection by exposure to SARS-CoV-2 virus in the air. One-sentence summaryA Fc-modified human antibody prevents SARS-CoV-2 viral infection via nasal administration

bioengineering↗