当前位置： SCI文献检索 > Nature Communications期刊下所有文献 > Highly efficient multiplex human T cell engineering without double-strand breaks using Cas9 base editors.

Highly efficient multiplex human T cell engineering without double-strand breaks using Cas9 base editors.

Abstract：

:The fusion of genome engineering and adoptive cellular therapy holds immense promise for the treatment of genetic disease and cancer. Multiplex genome engineering using targeted nucleases can be used to increase the efficacy and broaden the application of such therapies but carries safety risks associated with unintended genomic alterations and genotoxicity. Here, we apply base editor technology for multiplex gene modification in primary human T cells in support of an allogeneic CAR-T platform and demonstrate that base editor can mediate highly efficient multiplex gene disruption with minimal double-strand break induction. Importantly, multiplex base edited T cells exhibit improved expansion and lack double strand break-induced translocations observed in T cells edited with Cas9 nuclease. Our findings highlight base editor as a powerful platform for genetic modification of therapeutically relevant primary cell types.

journal_name

Nat Commun

journal_title

Nature communications

authors

Webber BR,Lonetree CL,Kluesner MG,Johnson MJ,Pomeroy EJ,Diers MD,Lahr WS,Draper GM,Slipek NJ,Smeester BA,Lovendahl KN,McElroy AN,Gordon WR,Osborn MJ,Moriarity BS

doi

10.1038/s41467-019-13007-6

subject

Has Abstract

pub_date

2019-11-19 00:00:00

pages

5222

issue

1

issn

2041-1723

pii

10.1038/s41467-019-13007-6

journal_volume

10

pub_type

杂志文章

相关文献

Nature Communications文献大全
  • Co-evolution of primitive methane-cycling ecosystems and early Earth's atmosphere and climate.

    abstract：:The history of the Earth has been marked by major ecological transitions, driven by metabolic innovation, that radically reshaped the composition of the oceans and atmosphere. The nature and magnitude of the earliest transitions, hundreds of million years before photosynthesis evolved, remain poorly understood. Using ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-16374-7

    authors： Sauterey B,Charnay B,Affholder A,Mazevet S,Ferrière R

    更新日期：2020-06-01 00:00:00

  • Closing the gap between palaeontological and neontological speciation and extinction rate estimates.

    abstract：:Measuring the pace at which speciation and extinction occur is fundamental to understanding the origin and evolution of biodiversity. Both the fossil record and molecular phylogenies of living species can provide independent estimates of speciation and extinction rates, but often produce strikingly divergent results. ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-07622-y

    authors： Silvestro D,Warnock RCM,Gavryushkina A,Stadler T

    更新日期：2018-12-07 00:00:00

  • All-optical design for inherently energy-conserving reversible gates and circuits.

    abstract：:As energy efficiency becomes a paramount issue in this day and age, reversible computing may serve as a critical step towards energy conservation in information technology. The inputs of reversible computing elements define the outputs and vice versa. Some reversible gates such as the Fredkin gate are also universal; ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms11424

    authors： Cohen E,Dolev S,Rosenblit M

    更新日期：2016-04-26 00:00:00

  • Terahertz field control of in-plane orbital order in La(0.5)Sr(1.5)MnO4.

    abstract：:In-plane anisotropic ground states are ubiquitous in correlated solids such as pnictides, cuprates and manganites. They can arise from doping Mott insulators and compete with phases such as superconductivity; however, their origins are debated. Strong coupling between lattice, charge, orbital and spin degrees of freed...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms9175

    authors： Miller TA,Chhajlany RW,Tagliacozzo L,Green B,Kovalev S,Prabhakaran D,Lewenstein M,Gensch M,Wall S

    更新日期：2015-09-18 00:00:00

  • Composite functional metasurfaces for multispectral achromatic optics.

    abstract：:Nanostructured metasurfaces offer unique capabilities for subwavelength control of optical waves. Based on this potential, a large number of metasurfaces have been proposed recently as alternatives to standard optical elements. In most cases, however, these elements suffer from large chromatic aberrations, thus limiti...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms14992

    authors： Avayu O,Almeida E,Prior Y,Ellenbogen T

    更新日期：2017-04-05 00:00:00

  • Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction.

    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

    authors： Ito S,Magalska A,Alcaraz-Iborra M,Lopez-Atalaya JP,Rovira V,Contreras-Moreira B,Lipinski M,Olivares R,Martinez-Hernandez J,Ruszczycki B,Lujan R,Geijo-Barrientos E,Wilczynski GM,Barco A

    更新日期：2014-07-18 00:00:00

  • Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer.

    abstract：:Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) gen...

    journal_title：Nature communications

    pub_type： 杂志文章,meta分析

    doi：10.1038/s41467-020-16711-w

    authors： Lin Y,Nakatochi M,Hosono Y,Ito H,Kamatani Y,Inoko A,Sakamoto H,Kinoshita F,Kobayashi Y,Ishii H,Ozaka M,Sasaki T,Matsuyama M,Sasahira N,Morimoto M,Kobayashi S,Fukushima T,Ueno M,Ohkawa S,Egawa N,Kuruma S,Mori M,

    更新日期：2020-06-24 00:00:00

  • SNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex to mediate Wntless sorting and Wnt secretion.

    abstract：:Wntless transports Wnt morphogens to the cell surface and is required for Wnt secretion and morphogenic gradients formation. Recycling of endocytosed Wntless requires the sorting nexin-3 (SNX3)-retromer-dependent endosome-to-Golgi transport pathway. Here we demonstrate the essential role of SNX3-retromer assembly for ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-06114-3

    authors： McGough IJ,de Groot REA,Jellett AP,Betist MC,Varandas KC,Danson CM,Heesom KJ,Korswagen HC,Cullen PJ

    更新日期：2018-09-13 00:00:00

  • ERG induces taxane resistance in castration-resistant prostate cancer.

    abstract：:Taxanes are the only chemotherapies used to treat patients with metastatic castration-resistant prostate cancer (CRPC). Despite the initial efficacy of taxanes in treating CRPC, all patients ultimately fail due to the development of drug resistance. In this study, we show that ERG overexpression in in vitro and in viv...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms6548

    authors： Galletti G,Matov A,Beltran H,Fontugne J,Miguel Mosquera J,Cheung C,MacDonald TY,Sung M,O'Toole S,Kench JG,Suk Chae S,Kimovski D,Tagawa ST,Nanus DM,Rubin MA,Horvath LG,Giannakakou P,Rickman DS

    更新日期：2014-11-25 00:00:00

  • Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network.

    abstract：:Understanding how evolution of antimicrobial resistance increases resistance to other drugs is a challenge of profound importance. By combining experimental evolution and genome sequencing of 63 laboratory-evolved lines, we charted a map of cross-resistance interactions between antibiotics in Escherichia coli, and exp...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms5352

    authors： Lázár V,Nagy I,Spohn R,Csörgő B,Györkei Á,Nyerges Á,Horváth B,Vörös A,Busa-Fekete R,Hrtyan M,Bogos B,Méhi O,Fekete G,Szappanos B,Kégl B,Papp B,Pál C

    更新日期：2014-07-08 00:00:00

  • Author Correction: Resonant out-of-phase fluorescence microscopy and remote imaging overcome spectral limitations.

    abstract：:The Peer Review File associated with this Article was updated shortly after publication to redact from the authors' point-by-point response a description of unpublished work describing how Speed OPIOM may in future be used to facilitate discrimination between FRET and direct excitation. ...

    journal_title：Nature communications

    pub_type： 杂志文章,已发布勘误

    doi：10.1038/s41467-017-02133-8

    authors： Quérard J,Zhang R,Kelemen Z,Plamont MA,Xie X,Chouket R,Roemgens I,Korepina Y,Albright S,Ipendey E,Volovitch M,Sladitschek HL,Neveu P,Gissot L,Gautier A,Faure JD,Croquette V,Le Saux T,Jullien L

    更新日期：2017-12-14 00:00:00

  • Actin-based confinement of calcium responses during Shigella invasion.

    abstract：:Shigella, the agent of bacillary dysentery, invades epithelial cells by locally inducing actin reorganization. Upon cell invasion, Shigella induces calcium (Ca(2+)) signalling, but its role in invasion has remained unclear. Here we show that components involved in inositol 1, 4, 5- trisphosphate (InsP3) signalling are...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms2561

    authors： Tran Van Nhieu G,Kai Liu B,Zhang J,Pierre F,Prigent S,Sansonetti P,Erneux C,Kuk Kim J,Suh PG,Dupont G,Combettes L

    更新日期：2013-01-01 00:00:00

  • Author Correction: Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels.

    abstract：:The original version of this Article contained an error in the spelling of the author David Bulkley, which was incorrectly given as David Bulkey. This has now 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/s41467-019-09422-4

    authors： Zheng W,Yang X,Hu R,Cai R,Hofmann L,Wang Z,Hu Q,Liu X,Bulkley D,Yu Y,Tang J,Flockerzi V,Cao Y,Cao E,Chen XZ

    更新日期：2019-03-26 00:00:00

  • Clustering of arc volcanoes caused by temperature perturbations in the back-arc mantle.

    abstract：:Clustering of arc volcanoes in subduction zones indicates along-arc variation in the physical condition of the underlying mantle where majority of arc magmas are generated. The sub-arc mantle is brought in from the back-arc largely by slab-driven mantle wedge flow. Dynamic processes in the back-arc, such as small-scal...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms15753

    authors： Lee C,Wada I

    更新日期：2017-06-29 00:00:00

  • Structure of the processive human Pol δ holoenzyme.

    abstract：:In eukaryotes, DNA polymerase δ (Pol δ) bound to the proliferating cell nuclear antigen (PCNA) replicates the lagging strand and cooperates with flap endonuclease 1 (FEN1) to process the Okazaki fragments for their ligation. We present the high-resolution cryo-EM structure of the human processive Pol δ-DNA-PCNA comple...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-14898-6

    authors： Lancey C,Tehseen M,Raducanu VS,Rashid F,Merino N,Ragan TJ,Savva CG,Zaher MS,Shirbini A,Blanco FJ,Hamdan SM,De Biasio A

    更新日期：2020-02-28 00:00:00

  • An autonomous DNA nanomachine maps spatiotemporal pH changes in a multicellular living organism.

    abstract：:Structural DNA nanotechnology seeks to build synthetic molecular machinery from DNA. DNA nanomachines are artificially designed assemblies that switch between defined conformations in response to an external cue. Though it has proved possible to create DNA machines and rudimentary walkers, the function of such autonom...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms1340

    authors： Surana S,Bhat JM,Koushika SP,Krishnan Y

    更新日期：2011-06-07 00:00:00

  • Stretching fibronectin fibres disrupts binding of bacterial adhesins by physically destroying an epitope.

    abstract：:Although soluble inhibitors are frequently used to block cell binding to the extracellular matrix (ECM), mechanical stretching of a protein fibre alone can physically destroy a cell-binding site. Here, we show using binding assays and steered molecular dynamics that mechanical tension along fibronectin (Fn) fibres cau...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms1135

    authors： Chabria M,Hertig S,Smith ML,Vogel V

    更新日期：2010-01-01 00:00:00

  • Imaging dynamic fingerprints of competing E2 and SN2 reactions.

    abstract：:The competition between bimolecular nucleophilic substitution and base-induced elimination is of fundamental importance for the synthesis of pure samples in organic chemistry. Many factors that influence this competition have been identified over the years, but the underlying atomistic dynamics have remained difficult...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-017-00065-x

    authors： Carrascosa E,Meyer J,Zhang J,Stei M,Michaelsen T,Hase WL,Yang L,Wester R

    更新日期：2017-06-21 00:00:00

  • Endocrine disruptors induce perturbations in endoplasmic reticulum and mitochondria of human pluripotent stem cell derivatives.

    abstract：:Persistent exposure to man-made endocrine disrupting chemicals during fetal endocrine development may lead to disruption of metabolic homeostasis contributing to childhood obesity. Limited cellular platforms exist to test endocrine disrupting chemical-induced developmental abnormalities in human endocrine tissues. Her...

    journal_title：Nature communications

    pub_type： 杂志文章,收录出版

    doi：10.1038/s41467-017-00254-8

    authors： Rajamani U,Gross AR,Ocampo C,Andres AM,Gottlieb RA,Sareen D

    更新日期：2017-08-09 00:00:00

  • Publisher Correction: Unveiling the Re effect in Ni-based single crystal superalloys.

    abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title：Nature communications

    pub_type： 已发布勘误

    doi：10.1038/s41467-020-14820-0

    authors： Wu X,Makineni SK,Liebscher CH,Dehm G,Mianroodi JR,Shanthraj P,Svendsen B,Bürger D,Eggeler G,Raabe D,Gault B

    更新日期：2020-02-21 00:00:00

  • AGO-bound mature miRNAs are oligouridylated by TUTs and subsequently degraded by DIS3L2.

    abstract：:MicroRNAs (miRNAs) associated with Argonaute proteins (AGOs) regulate gene expression in mammals. miRNA 3' ends are subject to frequent sequence modifications, which have been proposed to affect miRNA stability. However, the underlying mechanism is not well understood. Here, by genetic and biochemical studies as well ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-16533-w

    authors： Yang A,Shao TJ,Bofill-De Ros X,Lian C,Villanueva P,Dai L,Gu S

    更新日期：2020-06-02 00:00:00

  • Genome-scale proteome quantification by DEEP SEQ mass spectrometry.

    abstract：:Advances in chemistry and massively parallel detection underlie DNA-sequencing platforms that are poised for application in personalized medicine. In stark contrast, systematic generation of protein-level data lags well behind genomics in virtually every aspect: depth of coverage, throughput, ease of sample preparatio...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms3171

    authors： Zhou F,Lu Y,Ficarro SB,Adelmant G,Jiang W,Luckey CJ,Marto JA

    更新日期：2013-01-01 00:00:00

  • Variability in the location of high frequency oscillations during prolonged intracranial EEG recordings.

    abstract：:The rate of interictal high frequency oscillations (HFOs) is a promising biomarker of the seizure onset zone, though little is known about its consistency over hours to days. Here we test whether the highest HFO-rate channels are consistent across different 10-min segments of EEG during sleep. An automated HFO detecto...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-04549-2

    authors： Gliske SV,Irwin ZT,Chestek C,Hegeman GL,Brinkmann B,Sagher O,Garton HJL,Worrell GA,Stacey WC

    更新日期：2018-06-01 00:00:00

  • Oscillatory integration windows in neurons.

    abstract：:Oscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms13808

    authors： Gupta N,Singh SS,Stopfer M

    更新日期：2016-12-15 00:00:00

  • Gfi1b regulates the level of Wnt/β-catenin signaling in hematopoietic stem cells and megakaryocytes.

    abstract：:Gfi1b is a transcriptional repressor expressed in hematopoietic stem cells (HSCs) and megakaryocytes (MKs). Gfi1b deficiency leads to expansion of both cell types and abrogates the ability of MKs to respond to integrin. Here we show that Gfi1b forms complexes with β-catenin, its co-factors Pontin52, CHD8, TLE3 and CtB...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-09273-z

    authors： Shooshtarizadeh P,Helness A,Vadnais C,Brouwer N,Beauchemin H,Chen R,Bagci H,Staal FJT,Coté JF,Möröy T

    更新日期：2019-03-20 00:00:00

  • New Blatter-type radicals from a bench-stable carbene.

    abstract：:Stable benzotriazinyl radicals (Blatter's radicals) recently attracted considerable interest as building blocks for functional materials. The existing strategies to derivatize Blatter's radicals are limited, however, and synthetic routes are complex. Here, we report that an inexpensive, commercially available, analyti...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms15088

    authors： Grant JA,Lu Z,Tucker DE,Hockin BM,Yufit DS,Fox MA,Kataky R,Chechik V,O'Donoghue AC

    更新日期：2017-05-15 00:00:00

  • Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails.

    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

    authors： Dutertre S,Jin AH,Vetter I,Hamilton B,Sunagar K,Lavergne V,Dutertre V,Fry BG,Antunes A,Venter DJ,Alewood PF,Lewis RJ

    更新日期：2014-03-24 00:00:00

  • Overcurvature describes the buckling and folding of rings from curved origami to foldable tents.

    abstract：:Daily-life foldable items, such as popup tents, the curved origami sculptures exhibited in the Museum of Modern Art of New York, overstrained bicycle wheels, released bilayered microrings and strained cyclic macromolecules, are made of rings buckled or folded in tridimensional saddle shapes. Surprisingly, despite thei...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms2311

    authors： Mouthuy PO,Coulombier M,Pardoen T,Raskin JP,Jonas AM

    更新日期：2012-01-01 00:00:00

  • Truncation and constitutive activation of the androgen receptor by diverse genomic rearrangements in prostate cancer.

    abstract：:Molecularly targeted therapies for advanced prostate cancer include castration modalities that suppress ligand-dependent transcriptional activity of the androgen receptor (AR). However, persistent AR signalling undermines therapeutic efficacy and promotes progression to lethal castration-resistant prostate cancer (CRP...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms13668

    authors： Henzler C,Li Y,Yang R,McBride T,Ho Y,Sprenger C,Liu G,Coleman I,Lakely B,Li R,Ma S,Landman SR,Kumar V,Hwang TH,Raj GV,Higano CS,Morrissey C,Nelson PS,Plymate SR,Dehm SM

    更新日期：2016-11-29 00:00:00

  • A number-based inventory of size-resolved black carbon particle emissions by global civil aviation.

    abstract：:With the rapidly growing global air traffic, the impacts of the black carbon (BC) in the aviation exhaust on climate, environment and public health are likely rising. The particle number and size distribution are crucial metrics for toxicological analysis and aerosol-cloud interactions. Here, a size-resolved BC partic...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-08491-9

    authors： Zhang X,Chen X,Wang J

    更新日期：2019-02-01 00:00:00