Transgenesis by lentiviral vectors: lack of gene silencing in mammalian embryonic stem cells and preimplantation embryos.

Abstract:

:The introduction of foreign genes into early mouse embryos and embryonic stem (ES) cells is invaluable for the analysis of gene function and regulation in the living animal. The use of vectors derived from retroviruses as gene transfer vehicles in this setting has had limited success because of silencing of transgene expression. Here, we show that vectors derived from lentiviruses, which are complex retroviruses, can efficiently deliver genes to murine ES cells and that transgene expression is stable during proliferation of undifferentiated ES cells. The transgene is expressed during differentiation of ES cells in vitro (embryoid bodies) and in vivo (teratomas). Transfer of lentivector-transduced ES cells into blastocysts resulted in chimeric animals that expressed the transgene in multiple tissues. Embryos derived from crossings of chimeric mice expressed the transgene, indicating successful germ-line transmission. Infection of murine preimplantation embryos at morula stage with lentiviral vectors resulted in stable transduction and expression of the transgene in mouse embryos and in newborn mice. Finally, human ES cells were transduced by lentiviral vectors and expressed the transgene over several passages. Thus, lentiviral vectors represent a significant improvement over oncoretroviral vectors used previously for gene transfer into murine ES cells and preimplantation embryos. Ability to transfer foreign genes into human ES cells has potential relevance for the development of gene and cell-based therapies.

authors

Pfeifer A,Ikawa M,Dayn Y,Verma IM

doi

10.1073/pnas.251682798

keywords:

subject

Has Abstract

pub_date

2002-02-19 00:00:00

pages

2140-5

issue

4

eissn

0027-8424

issn

1091-6490

pii

99/4/2140

journal_volume

99

pub_type

杂志文章
  • In vitro trimerization of OmpF porin secreted by spheroplasts of Escherichia coli.

    abstract::It is not yet clear how bacterial outer membrane proteins reach their correct destination after they are secreted across the cytoplasmic membrane. We show here that porin OmpF is secreted into the medium as a water-soluble monomeric protein by spheroplasts of Escherichia coli. Furthermore, this monomeric porin is take...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.2.743

    authors: Sen K,Nikaido H

    更新日期:1990-01-01 00:00:00

  • The vertical occipital fasciculus: a century of controversy resolved by in vivo measurements.

    abstract::The vertical occipital fasciculus (VOF) is the only major fiber bundle connecting dorsolateral and ventrolateral visual cortex. Only a handful of studies have examined the anatomy of the VOF or its role in cognition in the living human brain. Here, we trace the contentious history of the VOF, beginning with its origin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.1418503111

    authors: Yeatman JD,Weiner KS,Pestilli F,Rokem A,Mezer A,Wandell BA

    更新日期:2014-12-02 00:00:00

  • Structural characterization of H-2 antigens purified from mouse liver.

    abstract::Papain solubilized H-2a histocompatibility antigens (H-2Kk plus H-2Dd) have been purified by a large-scale procedure that can routinely provide 2-3 mg of heavy chain from 1 kg of mouse liver. The heavy chains were homogeneous by sodium dodecyl sulfate electrophoresis. Disc gel electrophoresis resolved two protein band...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.7.3322

    authors: Henriksen O,Robinson EA,Appella E

    更新日期:1978-07-01 00:00:00

  • Third-generation synchrotron x-ray diffraction of 6-microm crystal of raite, approximately Na3Mn3Ti0.25Si8O20(OH)2.10H2O, opens up new chemistry and physics of low-temperature minerals.

    abstract::The crystal structure of raite was solved and refined from data collected at Beamline Insertion Device 13 at the European Synchrotron Radiation Facility, using a 3 x 3 x 65 microm single crystal. The refined lattice constants of the monoclinic unit cell are a = 15.1(1) A; b = 17.6(1) A; c = 5.290(4) A; beta = 100.5(2)...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.23.12263

    authors: Pluth JJ,Smith JV,Pushcharovsky DY,Semenov EI,Bram A,Riekel C,Weber HP,Broach RW

    更新日期:1997-11-11 00:00:00

  • Using microsecond single-molecule FRET to determine the assembly pathways of T4 ssDNA binding protein onto model DNA replication forks.

    abstract::DNA replication is a core biological process that occurs in prokaryotic cells at high speeds (∼1 nucleotide residue added per millisecond) and with high fidelity (fewer than one misincorporation event per 107 nucleotide additions). The ssDNA binding protein [gene product 32 (gp32)] of the T4 bacteriophage is a central...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1619819114

    authors: Phelps C,Israels B,Jose D,Marsh MC,von Hippel PH,Marcus AH

    更新日期:2017-05-02 00:00:00

  • The primary structure of sensory rhodopsin II: a member of an additional retinal protein subgroup is coexpressed with its transducer, the halobacterial transducer of rhodopsin II.

    abstract::The blue-light receptor genes (sopII) of sensory rhodopsin (SR) II were cloned from two species, the halophilic bacteria Haloarcula vallismortis (vSR-II) and Natronobacterium pharaonis (pSR-II). Upstream of both sopII gene loci, sequences corresponding to the halobacterial transducer of rhodopsin (Htr) II were recogni...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.7.3036

    authors: Seidel R,Scharf B,Gautel M,Kleine K,Oesterhelt D,Engelhard M

    更新日期:1995-03-28 00:00:00

  • Bacterial peptide chain release factors: conserved primary structure and possible frameshift regulation of release factor 2.

    abstract::Escherichia coli peptide chain release factors are proteins that direct the termination of translation in response to specific peptide chain termination codons. The mechanisms of codon recognition and peptidyl-tRNA hydrolysis are unknown. We have characterized the genes encoding release factor 1 (RF-1) and release fac...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.11.3616

    authors: Craigen WJ,Cook RG,Tate WP,Caskey CT

    更新日期:1985-06-01 00:00:00

  • A major calmodulin-binding protein common to various vertebrate tissues.

    abstract::A major calmodulin-binding protein (CaM-BP) of Mr 240,000 was demonstrated in various rat tissues by using a 125I-labeled CaM gel overlay technique. This protein (designated p240) was detected in the particulate fraction and to a lesser extent in the cytosol of all tissues studied. Binding of CaM to p240 was completel...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.12.3780

    authors: Palfrey HC,Schiebler W,Greengard P

    更新日期:1982-06-01 00:00:00

  • Dominant hemisphere lateralization of cortical parasympathetic control as revealed by frontotemporal dementia.

    abstract::The brain continuously influences and perceives the physiological condition of the body. Related cortical representations have been proposed to shape emotional experience and guide behavior. Although previous studies have identified brain regions recruited during autonomic processing, neurological lesion studies have ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1509184113

    authors: Guo CC,Sturm VE,Zhou J,Gennatas ED,Trujillo AJ,Hua AY,Crawford R,Stables L,Kramer JH,Rankin K,Levenson RW,Rosen HJ,Miller BL,Seeley WW

    更新日期:2016-04-26 00:00:00

  • Demonstration of biological activity of brain gastrin-like peptidic material in the human: its relationship with the COOH-terminal octapeptide of cholecystokinin.

    abstract::The previously described peptide material that reacts with antibodies to gastrin and is found in the central nervous system of various vertebrates is present in only the 100,000 X g pellet of postmortem human cerebral cortical grey matter. This immunoreactive material, extractable in boiling water, is biologically act...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.1.524

    authors: Robberecht P,Deschodt-Lanckman M,Vanderhaeghen JJ

    更新日期:1978-01-01 00:00:00

  • Molecular random tilings as glasses.

    abstract::We have recently shown that p-terphenyl-3,5,3',5'-tetracarboxylic acid adsorbed on graphite self-assembles into a two-dimensional rhombus random tiling. This tiling is close to ideal, displaying long-range correlations punctuated by sparse localized tiling defects. In this article we explore the analogy between dynami...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0902443106

    authors: Garrahan JP,Stannard A,Blunt MO,Beton PH

    更新日期:2009-09-08 00:00:00

  • Differential regulation of type III secretion and virulence genes in Bordetella pertussis and Bordetella bronchiseptica by a secreted anti-σ factor.

    abstract::The BvgAS phosphorelay regulates ∼10% of the annotated genomes of Bordetella pertussis and Bordetella bronchiseptica and controls their infectious cycles. The hierarchical organization of the regulatory network allows the integration of contextual signals to control all or specific subsets of BvgAS-regulated genes. He...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1600320113

    authors: Ahuja U,Shokeen B,Cheng N,Cho Y,Blum C,Coppola G,Miller JF

    更新日期:2016-03-01 00:00:00

  • Synthesis of the next-generation therapeutic antibodies that combine cell targeting and antibody-catalyzed prodrug activation.

    abstract::An obstacle in the utilization of catalytic Abs for selective prodrug activation in cancer therapy has been systemic tumor targeting. Here we report the generation of catalytic Abs that effectively target tumor cells with undiminished prodrug activation capability. Ab conjugates were prepared by covalent conjugation o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0700223104

    authors: Abraham S,Guo F,Li LS,Rader C,Liu C,Barbas CF 3rd,Lerner RA,Sinha SC

    更新日期:2007-03-27 00:00:00

  • Functional coupling of Ca2+ channels and ryanodine receptors in cardiac myocytes.

    abstract::In skeletal muscle, dihydropyridine receptors are functionally coupled to ryanodine receptors of the sarcoplasmic reticulum in triadic or diadic junctional complexes. In cardiac muscle direct physical or functional couplings have not been demonstrated. We have tested the hypothesis of functional coupling of L-type Ca2...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.1.121

    authors: Sham JS,Cleemann L,Morad M

    更新日期:1995-01-03 00:00:00

  • A coherent framework for multiresolution analysis of biological networks with "memory": Ras pathway, cell cycle, and immune system.

    abstract::Various biological processes exhibit characteristics that vary dramatically in response to different input conditions or changes in the history of the process itself. One of the examples studied here, the Ras-PKC-mitogen-activated protein kinase (MAPK) bistable pathway, follows two distinct dynamics (modes) depending ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0500554102

    authors: Barbano PE,Spivak M,Feng J,Antoniotti M,Mishra B

    更新日期:2005-05-03 00:00:00

  • Specific interaction between a Saccharomyces cerevisiae protein and a DNA element associated with certain autonomously replicating sequences.

    abstract::We have isolated a protein from Saccharomyces cerevisiae that binds specifically to a nucleotide sequence associated with the autonomously replicating sequence (ARS) ARS120, located in the telomeric region of a yeast chromosome. "Footprinting" analysis revealed that a 26-base-pair DNA sequence, 5'-CAAGTGCCGTGCATAATGAT...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.3.743

    authors: Eisenberg S,Civalier C,Tye BK

    更新日期:1988-02-01 00:00:00

  • Dialyzable factor in human serum of platelet origin stimulates endothelial cell replication and growth.

    abstract::Porcine aortic endothelial cells were isolated and maintained in Dulbecco's modified Eagle's medium (DME medium)/10% citrate-treated human plasma. They were stimulated by DME medium/10% human serum to grow from a density of 10,100 +/- 500 per well to a final density of 83,000 +/- 1,800 per well over a 9-day period. On...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.6.1641

    authors: Clemmons DR,Isley WL,Brown MT

    更新日期:1983-03-01 00:00:00

  • Interaction instability of localization in quasiperiodic systems.

    abstract::Integrable models form pillars of theoretical physics because they allow for full analytical understanding. Despite being rare, many realistic systems can be described by models that are close to integrable. Therefore, an important question is how small perturbations influence the behavior of solvable models. This is ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1800589115

    authors: Žnidarič M,Ljubotina M

    更新日期:2018-05-01 00:00:00

  • Functional analysis of an oxygen-regulated transcriptional enhancer lying 3' to the mouse erythropoietin gene.

    abstract::Erythropoietin, the major hormone controlling red-cell production, is regulated in part through oxygen-dependent changes in the rate of transcription of its gene. Using transient transfection in HepG2 cells, we have defined a DNA sequence, located 120 base pairs 3' to the poly(A)-addition site of the mouse erythropoie...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.23.10553

    authors: Pugh CW,Tan CC,Jones RW,Ratcliffe PJ

    更新日期:1991-12-01 00:00:00

  • Individual products of the adenovirus 12S and 13S EIa mRNAs stimulate viral EIIa and EIII expression at the transcriptional level.

    abstract::Recombinant plasmids containing mutant or wild-type adenovirus serotype 2 EIa genes that produce the 12S mRNA alone, the 13S mRNA alone, or both mRNAs were cotransfected into HeLa cells with plasmids containing the viral EIIa or EIII transcription units. The amount of RNA produced from the EIIa and EIII promoters was ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.14.4381

    authors: Leff T,Elkaim R,Goding CR,Jalinot P,Sassone-Corsi P,Perricaudet M,Kédinger C,Chambon P

    更新日期:1984-07-01 00:00:00

  • (1)O2-mediated retrograde signaling during late embryogenesis predetermines plastid differentiation in seedlings by recruiting abscisic acid.

    abstract::Plastid development in seedlings of Arabidopsis thaliana is affected by the transfer of (1)O(2)-mediated retrograde signals from the plastid to the nucleus and changes in nuclear gene expression during late embryogenesis. The potential impact of these mechanisms on plastid differentiation is maintained throughout seed...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0901315106

    authors: Kim C,Lee KP,Baruah A,Nater M,Göbel C,Feussner I,Apel K

    更新日期:2009-06-16 00:00:00

  • Interferon regulatory factor 4 differentially regulates the production of Th2 cytokines in naive vs. effector/memory CD4+ T cells.

    abstract::Interferon regulatory factor (IRF) 4 is a member of the IRF family of transcription factors and plays critical roles in the development of CD4(+) T cells into Th2 and Th17 cells. Using the infection model of Nippostrongyrus brasiliensis, we have confirmed the critical roles of IRF-4 in Th2 development in vivo by using...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0803171105

    authors: Honma K,Kimura D,Tominaga N,Miyakoda M,Matsuyama T,Yui K

    更新日期:2008-10-14 00:00:00

  • Evidence that spontaneous mitotic recombination occurs at the two-strand stage.

    abstract::Spontaneous reciprocal mitotic recombination in the yeast Saccharomyces cerevisiae, associated with heteroallelic recombination, occurs almost exclusively at the two-strand stage and involves recombination of unduplicated chromosomes (i.e., during G1) or the unduplicated regions of chromosomes during the S phase of mi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.9.4436

    authors: Esposito MS

    更新日期:1978-09-01 00:00:00

  • Self-enforcing strategies to deter free-riding in the climate change mitigation game and other repeated public good games.

    abstract::As the Copenhagen Accord indicates, most of the international community agrees that global mean temperature should not be allowed to rise more than two degrees Celsius above preindustrial levels to avoid unacceptable damages from climate change. The scientific evidence distilled in the Fourth Assessment Report of the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1106265108

    authors: Heitzig J,Lessmann K,Zou Y

    更新日期:2011-09-20 00:00:00

  • Speech-like cerebral activity in profoundly deaf people processing signed languages: implications for the neural basis of human language.

    abstract::For more than a century we have understood that our brain's left hemisphere is the primary site for processing language, yet why this is so has remained more elusive. Using positron emission tomography, we report cerebral blood flow activity in profoundly deaf signers processing specific aspects of sign language in ke...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.25.13961

    authors: Petitto LA,Zatorre RJ,Gauna K,Nikelski EJ,Dostie D,Evans AC

    更新日期:2000-12-05 00:00:00

  • Modulation of gamma-aminobutyric acid-mediated inhibitory synaptic currents in dissociated cortical cell cultures.

    abstract::Inhibitory gamma-aminobutyric acid-mediated synaptic currents were studied in dissociated primary cultures of neonatal rat cortex with the whole-cell patch-clamp technique. Immunocytochemical staining of the cultures showed the presence of a large number of glutamic acid decarboxylase-containing neurons, and electrica...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.23.9269

    authors: Vicini S,Alho H,Costa E,Mienville JM,Santi MR,Vaccarino FM

    更新日期:1986-12-01 00:00:00

  • Direct measurement of oligonucleotide substrate binding to wild-type and mutant ribozymes from Tetrahymena.

    abstract::Like protein enzymes, RNA enzymes (ribozymes) provide specific binding sites for their substrates. We now show that equilibrium dissociation constants for complexes between the Tetrahymena ribozyme and its RNA substrates and products can be directly measured by electrophoresis in polyacrylamide gels containing divalen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.21.8187

    authors: Pyle AM,McSwiggen JA,Cech TR

    更新日期:1990-11-01 00:00:00

  • The degree of extra-pair paternity increases with genetic variability.

    abstract::The amount of extra-pair paternity in socially monogamous bird species varies from 0% to 76% extra-pair offspring. The causes of this remarkable interspecific variation are largely unknown, although intraspecific analyses suggest that females seek extra-pair matings to improve the genetic quality of their offspring. I...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.16.9390

    authors: Petrie M,Doums C,Moller AP

    更新日期:1998-08-04 00:00:00

  • A semiquinone intermediate generated at the Qo site of the cytochrome bc1 complex: importance for the Q-cycle and superoxide production.

    abstract::The cytochrome bc1 and related complexes are essential energy-conserving components of mitochondrial and bacterial electron transport chains. They orchestrate a complex sequence of electron and proton transfer reactions resulting in the oxidation of quinol, the reduction of a mobile electron carrier, and the transloca...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0702621104

    authors: Cape JL,Bowman MK,Kramer DM

    更新日期:2007-05-08 00:00:00

  • Evidence that a second tumor antigen coded by adenovirus early gene region E1a is required for efficient cell transformation.

    abstract::The expression of the adenovirus (Ad) early coding region 1a (E1a) is required for virus-induced cell transformation and for the activation of other viral early genes and some cellular genes. Two overlapping early mRNAs of 13S and 12S that are transcribed from this region code for a 289-amino acid protein and a 243-am...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.1.163

    authors: Hurwitz DR,Chinnadurai G

    更新日期:1985-01-01 00:00:00