Abstract:
:A short half-life in the circulation limits the application of therapeutics such as single-domain antibodies (VHHs). We utilize red blood cells to prolong the circulatory half-life of VHHs. Here we present VHHs against botulinum neurotoxin A (BoNT/A) on the surface of red blood cells by expressing chimeric proteins of VHHs with Glycophorin A or Kell. Mice whose red blood cells carry the chimeric proteins exhibit resistance to 10,000 times the lethal dose (LD50) of BoNT/A, and transfusion of these red blood cells into naive mice affords protection for up to 28 days. We further utilize an improved CD34+ culture system to engineer human red blood cells that express these chimeric proteins. Mice transfused with these red blood cells are resistant to highly lethal doses of BoNT/A. We demonstrate that engineered red blood cells expressing VHHs can provide prolonged prophylactic protection against bacterial toxins without inducing inhibitory immune responses and illustrates the potentially broad translatability of our strategy for therapeutic applications.The therapeutic use of single-chain antibodies (VHHs) is limited by their short half-life in the circulation. Here the authors engineer mouse and human red blood cells to express VHHs against botulinum neurotoxin A (BoNT/A) on their surface and show that an infusion of these cells into mice confers long lasting protection against a high dose of BoNT/A.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Huang NJ,Pishesha N,Mukherjee J,Zhang S,Deshycka R,Sudaryo V,Dong M,Shoemaker CB,Lodish HFdoi
10.1038/s41467-017-00448-0subject
Has Abstractpub_date
2017-09-04 00:00:00pages
423issue
1issn
2041-1723pii
10.1038/s41467-017-00448-0journal_volume
8pub_type
杂志文章abstract::Aberrant splicing is frequently found in cancer, yet the biological consequences of such alterations are mostly undefined. Here we report that the Hippo-YAP signalling, a key pathway that regulates cell proliferation and organ size, is under control of a splicing switch. We show that TEAD4, the transcription factor th...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11840
更新日期:2016-06-13 00:00:00
abstract::The flexibility in structural design of organic semiconductors endows organic solar cells (OSCs) not only great function-tunabilities, but also high potential toward practical application. In this work, simple non-fused-ring electron acceptors are developed through two-step synthesis from single aromatic units for con...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-10098-z
更新日期:2019-05-14 00:00:00
abstract::The mammary gland experiences substantial remodeling and regeneration during development and reproductive life, facilitated by stem cells and progenitors that act in concert with physiological stimuli. While studies have focused on deciphering regenerative cells within the parenchymal epithelium, cell lineages in the ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-09748-z
更新日期:2019-04-15 00:00:00
abstract::Adeno-associated virus (AAV) capsid engineering is an emerging approach to advance gene therapy. However, a systematic analysis on how each capsid amino acid contributes to multiple functions remains challenging. Here we show proof-of-principle and successful application of a novel approach, termed AAV Barcode-Seq, th...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4075
更新日期:2014-01-01 00:00:00
abstract::Auditory cortex neurons nonlinearly integrate synaptic inputs from the thalamus and cortex, and generate spiking outputs for simple and complex sounds. Directly comparing synaptic and spiking activity can determine whether this input-output transformation is stimulus-dependent. We employ in vivo whole-cell recordings ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-14835-7
更新日期:2020-02-27 00:00:00
abstract::Collective cell migration mediates multiple tissue morphogenesis processes. Yet how multi-dimensional mesenchymal cell movements are coordinated remains mostly unknown. Here we report that coordinated mesenchymal cell migration during chicken feather elongation is accompanied by dynamic changes of bioelectric currents...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07661-5
更新日期:2018-12-18 00:00:00
abstract::In the originally published version of this Article, the affiliation details for Eric E. Schadt and Radoslav Savic incorrectly omitted 'Sema4, a Mount Sinai venture, Stamford, Connecticut, USA'. This has been corrected in both the PDF and HTML versions of the Article. ...
journal_title:Nature communications
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41467-018-07326-3
更新日期:2018-11-19 00:00:00
abstract::MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed 'small RNA zipper'. It is designed to connect miRNA molecules end to end, forming a DNA-RNA duplex through a complementary interaction with hi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13964
更新日期:2017-01-03 00:00:00
abstract::The human Immunodeficiency Centromeric Instability Facial Anomalies (ICF) 4 syndrome is a severe disease with increased mortality caused by mutation in the LSH gene. Although LSH belongs to a family of chromatin remodeling proteins, it remains unknown how LSH mediates its function on chromatin in vivo. Here, we use ch...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-19159-0
更新日期:2020-11-06 00:00:00
abstract::Piezo proteins are transmembrane ion channels which transduce many forms of mechanical stimuli into electrochemical signals. Their pore, formed by the assembly of three identical subunits, opens by an unknown mechanism. Here, to probe this mechanism, we investigate the interaction of Piezo1 with the small molecule ago...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-04405-3
更新日期:2018-05-23 00:00:00
abstract::DNA damage and secondary structures can stall the replication machinery. Cells possess numerous tolerance mechanisms to complete genome duplication in the presence of such impediments. In addition to translesion synthesis (TLS) polymerases, most eukaryotic cells contain a multifunctional replicative enzyme called prim...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms15222
更新日期:2017-05-23 00:00:00
abstract::Chronic cranial window (CCW) is an essential tool in enabling longitudinal imaging and manipulation of various brain activities in live animals. However, an active CCW capable of sensing the concealed in vivo environment while simultaneously providing longitudinal optical access to the brain is not currently available...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12178-6
更新日期:2019-09-19 00:00:00
abstract::The Lyme disease agent, Borrelia burgdorferi, colonizes the gut of the tick Ixodes scapularis, which transmits the pathogen to vertebrate hosts including humans. Here we show that B. burgdorferi colonization increases the expression of several tick gut genes including pixr, encoding a secreted gut protein with a Reele...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-00208-0
更新日期:2017-08-04 00:00:00
abstract::Overexpression of a drug's molecular target often increases drug resistance, offering a pathway for adaptive evolution and a tool for target identification. It is unclear though why this phenomenon applies to some drugs but not others. Here we gradually overexpressed antibiotic targets in Escherichia coli and found th...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms5296
更新日期:2014-07-01 00:00:00
abstract::The spindle assembly checkpoint (SAC) arrests cells in mitosis by sensing unattached kinetochores, until all chromosomes are bi-oriented by spindle microtubules. Kinetochore accumulation of the SAC component Mad1-Mad2 is crucial for SAC activation. However, the mechanism by which Mad1-Mad2 accumulation at kinetochores...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms10151
更新日期:2016-01-08 00:00:00
abstract::A correction to this article has been published and is linked from the HTML version of this article. ...
journal_title:Nature communications
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41467-017-01354-1
更新日期:2017-10-12 00:00:00
abstract::Venomous animals are thought to inject the same combination of toxins for both predation and defence, presumably exploiting conserved target pharmacology across prey and predators. Remarkably, cone snails can rapidly switch between distinct venoms in response to predatory or defensive stimuli. Here, we show that the d...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4521
更新日期:2014-03-24 00:00:00
abstract::The ability to understand and control the electronic properties of individual molecules in a device environment is crucial for developing future technologies at the nanometre scale and below. Achieving this, however, requires the creation of three-terminal devices that allow single molecules to be both gated and image...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13553
更新日期:2016-11-25 00:00:00
abstract::There is a critical need for standard approaches to assess, report and compare the technical performance of genome-scale differential gene expression experiments. Here we assess technical performance with a proposed standard 'dashboard' of metrics derived from analysis of external spike-in RNA control ratio mixtures. ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms6125
更新日期:2014-09-25 00:00:00
abstract::It has been suggested that deficient protein trafficking to the cell membrane is the dominant mechanism associated with type 2 Long QT syndrome (LQT2) caused by Kv11.1 potassium channel missense mutations, and that for many mutations the trafficking defect can be corrected pharmacologically. However, this inference wa...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms6535
更新日期:2014-11-24 00:00:00
abstract::Defensins are cationic antimicrobial peptides expressed throughout the plant and animal kingdoms as a first line of defense against pathogens. Membrane targeting and disruption is a crucial function of many defensins, however the precise mechanism remains unclear. Certain plant defensins form dimers that specifically ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-04434-y
更新日期:2018-05-17 00:00:00
abstract::Intensive studies have recently been performed on graphene-based photodetectors, but most of them are based on field effect transistor structures containing mechanically exfoliated graphene, not suitable for practical large-scale device applications. Here we report high-efficient photodetector behaviours of chemical v...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4249
更新日期:2014-01-01 00:00:00
abstract::Regulatory T (Treg) cells derived from the thymus (tTreg) and periphery (pTreg) have central and distinct functions in immunosuppression, but mechanisms for the generation and activation of Treg subsets in vivo are unclear. Here, we show that mechanistic target of rapamycin (mTOR) unexpectedly supports the homeostasis...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-04392-5
更新日期:2018-05-29 00:00:00
abstract::Metabolic reprogramming greatly contributes to the regulation of macrophage activation. However, the mechanism of lipid accumulation and the corresponding function in tumor-associated macrophages (TAMs) remain unclear. With primary investigation in colon cancer and confirmation in other cancer models, here we determin...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-04999-8
更新日期:2018-07-03 00:00:00
abstract::Akin to single-site homogeneous catalysis, a long sought-after goal is to achieve reaction site precision in heterogeneous catalysis for chemical control over patterns of activity, selectivity and stability. Herein, we report on metal phosphides as a class of material capable of realizing these attributes and unlock t...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-18943-2
更新日期:2020-10-13 00:00:00
abstract::Radiotherapy is not currently informed by the genetic composition of an individual patient's tumour. To identify genetic features regulating survival after DNA damage, here we conduct large-scale profiling of cellular survival after exposure to radiation in a diverse collection of 533 genetically annotated human tumou...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11428
更新日期:2016-04-25 00:00:00
abstract::Perovskite solar cells present one of the most prominent photovoltaic technologies, yet their stability, scalability, and engineering at the molecular level remain challenging. We demonstrate a concept of multifunctional molecular modulation of scalable and operationally stable perovskite solar cells that exhibit exce...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-06709-w
更新日期:2018-10-26 00:00:00
abstract::Haematopoietic stem cells (HSCs) are produced during embryogenesis from the floor of the dorsal aorta. The localization of HSCs is dependent on the presence of instructive signals on the ventral side of the vessel. The nature of the extrinsic molecular signals that control the aortic haematopoietic niche is currently ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms6588
更新日期:2014-11-27 00:00:00
abstract::The interior of the neuronal cell nucleus is a highly organized three-dimensional (3D) structure where regions of the genome that are linearly millions of bases apart establish sub-structures with specialized functions. To investigate neuronal chromatin organization and dynamics in vivo, we generated bitransgenic mice...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms5450
更新日期:2014-07-18 00:00:00
abstract::Currently, there is no comprehensive framework to evaluate the evolutionary forces acting on genomic regions associated with human complex traits and contextualize the relationship between evolution and molecular function. Here, we develop an approach to test for signatures of diverse evolutionary forces on trait-asso...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-17258-6
更新日期:2020-07-24 00:00:00