Delivery of antisense oligodeoxyribonucleotides against the human epidermal growth factor receptor into cultured KB cells with liposomes conjugated to folate via polyethylene glycol.

Abstract:

:Antisense oligodeoxyribonucleotides targeted to the epidermal growth factor (EGF) receptor were encapsulated into liposomes linked to folate via a polyethylene glycol spacer (folate-PEG-liposomes) and efficiently delivered into cultured KB cells via folate receptor-mediated endocytosis. The oligonucleotides were a phosphodiester 15-mer antisense to the EGF receptor (EGFR) gene stop codon (AEGFR2), the same sequence with three phosphorothioate linkages at each terminus (AEGFR2S), a randomized 15-mer control of similar base composition to AEGFR2 (RC15), a 14-mer control derived from a symmetrized Escherichia coli lac operator (LACM), and the 5'-fluorescein-labeled homologs of several of the above. Cellular uptake of AEGFR2 encapsulated in folate-PEG-liposomes was nine times higher than AEGFR2 encapsulated in nontargeted liposomes and 16 times higher than unencapsulated AEGFR2. Treatment of KB cells with AEGFR2 in folate-PEG-liposomes resulted in growth inhibition and significant morphological changes. Curiously, AEGFR2 and AEGFR2S encapsulated in folate-PEG-liposomes exhibited virtually identical growth inhibitory effects, reducing KB cell proliferation by > 90% 48 hr after the cells were treated for 4 hr with 3 microM oligonucleotide. Free AEGFR2 caused almost no growth inhibition, whereas free AEGFR2S was only one-fifth as potent as the folate-PEG-liposome-encapsulated oligonucleotide. Growth inhibition of the oligonucleotide-treated cells was probably due to reduced EGFR expression because indirect immunofluorescence staining of the cells with a monoclonal antibody against the EGFR showed an almost quantitative reduction of the EGFR in cells treated with folate-PEG-liposome-entrapped AEGFR2. These results suggest that antisense oligonucleotide encapsulation in folate-PEG-liposomes promise efficient and tumor-specific delivery and that phosphorothioate oligonucleotides appear to offer no major advantage over native phosphodiester DNA when delivered by this route.

authors

Wang S,Lee RJ,Cauchon G,Gorenstein DG,Low PS

doi

10.1073/pnas.92.8.3318

subject

Has Abstract

pub_date

1995-04-11 00:00:00

pages

3318-22

issue

8

eissn

0027-8424

issn

1091-6490

journal_volume

92

pub_type

杂志文章
  • Mechanisms underlying contrast-dependent orientation selectivity in mouse V1.

    abstract::Recent experiments have shown that mouse primary visual cortex (V1) is very different from that of cat or monkey, including response properties-one of which is that contrast invariance in the orientation selectivity (OS) of the neurons' firing rates is replaced in mouse with contrast-dependent sharpening (broadening) ...

    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.1719044115

    authors: Dai WP,Zhou D,McLaughlin DW,Cai D

    更新日期:2018-11-06 00:00:00

  • [3H]Phencyclidine: a probe for the ionic channel of the nicotinic receptor.

    abstract::To evaluate [3H]phencyclidine ([3H]PCP)as a probe for the ionic channel of the nicotinic receptor, the characteristics of its binding to electric organ membranes od Torpedo ocellata and its effects on frog sartorius muscle were studied. Similar to PCP, [3H]PCP depressed the peak amplitude of endplate current, caused n...

    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.77.12.7458

    authors: Eldefrawi ME,Eldefrawi AT,Aronstam RS,Maleque MA,Warnick JE,Albuquerque EX

    更新日期:1980-12-01 00:00:00

  • Nucleotide sequence analysis of feline immunodeficiency virus: genome organization and relationship to other lentiviruses.

    abstract::We determined the complete nucleotide sequence of an infectious proviral molecular clone (FIV-14) of the feline immunodeficiency virus (FIV). FIV-14 has a genome organization similar in complexity to other lentiviruses. In addition to three large open reading frames representing the gag, pol, and env genes, at least f...

    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.86.20.8088

    authors: Olmsted RA,Hirsch VM,Purcell RH,Johnson PR

    更新日期:1989-10-01 00:00:00

  • miR-155 targets histone deacetylase 4 (HDAC4) and impairs transcriptional activity of B-cell lymphoma 6 (BCL6) in the Eμ-miR-155 transgenic mouse model.

    abstract::Multiple studies have established that microRNAs (miRNAs) are involved in the initiation and progression of cancer. Notably, miR-155 is one of the most overexpressed miRNAs in several solid and hematological malignancies. Ectopic miR-155 expression in mice B cells (Eμ-miR-155 transgenic mice) has been shown to induce ...

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

    pub_type: 杂志文章,meta分析

    doi:10.1073/pnas.1213764109

    authors: Sandhu SK,Volinia S,Costinean S,Galasso M,Neinast R,Santhanam R,Parthun MR,Perrotti D,Marcucci G,Garzon R,Croce CM

    更新日期:2012-12-04 00:00:00

  • Inhibition of glycolate and D-lactate metabolism in a Chlamydomonas reinhardtii mutant deficient in mitochondrial respiration.

    abstract::The possibility that glycolate oxidation in unicellular green algae is linked to mitochondrial electron transport, rather than to peroxisomal metabolism as in higher plants and animals, was studied in a mutant of Chlamydomonas reinhardtii (dk97) deficient in cytochrome oxidase. This mutant had normal rates of dark res...

    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.84.6.1555

    authors: Husic DW,Tolbert NE

    更新日期:1987-03-01 00:00:00

  • From the Cover: Neutralization of terminal differentiation in gliomagenesis.

    abstract::An immature state of cellular differentiation--characterized by stem cell-like tendencies and impaired differentiation--is a hallmark of cancer. Using glioblastoma multiforme (GBM) as a model system, we sought to determine whether molecular determinants that drive cells toward terminal differentiation are also genetic...

    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.1308610110

    authors: Hu J,Ho AL,Yuan L,Hu B,Hua S,Hwang SS,Zhang J,Hu T,Zheng H,Gan B,Wu G,Wang YA,Chin L,DePinho RA

    更新日期:2013-09-03 00:00:00

  • Experience-dependent changes in cerebellar contributions to motor sequence learning.

    abstract::Studies in experimental animals and humans have stressed the role of the cerebellum in motor skill learning. Yet, the relative importance of the cerebellar cortex and deep nuclei, as well as the nature of the dynamic functional changes occurring between these and other motor-related structures during learning, remains...

    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.022615199

    authors: Doyon J,Song AW,Karni A,Lalonde F,Adams MM,Ungerleider LG

    更新日期:2002-01-22 00:00:00

  • Lon-dependent regulation of the DNA binding protein HU in Escherichia coli.

    abstract::HU, the major DNA binding protein of Escherichia coli, exists in solution as a heterodimer composed of two highly homologous subunits: HU1, encoded by hupB; HU2, encoded by hupA. The purification of the HU protein from hupA- or hupB- bacteria showed that the hupB mutant strains synthesize normal amounts of the HU2 sub...

    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.86.20.7691

    authors: Bonnefoy E,Almeida A,Rouviere-Yaniv J

    更新日期:1989-10-01 00:00:00

  • JNK and decapentaplegic signaling control adhesiveness and cytoskeleton dynamics during thorax closure in Drosophila.

    abstract::One of the fundamental events in metamorphosis in insects is the replacement of larval tissues by imaginal tissues. Shortly after pupariation the imaginal discs evaginate to assume their positions at the surface of the prepupal animal. This is a very precise process that is only beginning to be understood. In Drosophi...

    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.97.14.7888

    authors: Martin-Blanco E,Pastor-Pareja JC,Garcia-Bellido A

    更新日期:2000-07-05 00:00:00

  • A second wave of Sonic hedgehog expression during the development of the bat limb.

    abstract::Sonic hedgehog (Shh) plays an integral role in both the anterior-posterior (A-P) patterning and expansion of developing vertebrate limbs through a feedback loop involving Fgfs, Bmps, and Gremlin. In bat limbs A-P patterning and the size of the digital field are unique. The posterior digits of the forelimb are elongate...

    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.0805308105

    authors: Hockman D,Cretekos CJ,Mason MK,Behringer RR,Jacobs DS,Illing N

    更新日期:2008-11-04 00:00:00

  • A new class of Escherichia coli recBC mutants: implications for the role of RecBC enzyme in homologous recombination.

    abstract::Mutants of Escherichia coli sensitive to phage T4 gene 2 mutants were obtained following ethyl methanesulfonate mutagenesis. By mapping and complementation analysis, the mutations in each of the six mutants are in recB and recC. By both in vivo and in vitro analyses, the nuclease activity of RecBC enzyme is undetectab...

    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.81.24.7850

    authors: Chaudhury AM,Smith GR

    更新日期:1984-12-01 00:00:00

  • The Na+/I symporter (NIS) mediates electroneutral active transport of the environmental pollutant perchlorate.

    abstract::The Na(+)/I(-) symporter (NIS) is a key plasma membrane protein that mediates active I(-) uptake in the thyroid, lactating breast, and other tissues with an electrogenic stoichiometry of 2 Na(+) per I(-). In the thyroid, NIS-mediated I(-) uptake is the first step in the biosynthesis of the iodine-containing thyroid ho...

    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.0707207104

    authors: Dohán O,Portulano C,Basquin C,Reyna-Neyra A,Amzel LM,Carrasco N

    更新日期:2007-12-18 00:00:00

  • Mutation eliminating mitochondrial leader sequence of methylmalonyl-CoA mutase causes muto methylmalonic acidemia.

    abstract::Methylmalonyl-CoA mutase (EC 5.4.99.2) is a mitochondrial matrix enzyme whose activity is deficient in the inherited disorder methylmalonic acidemia. Previous studies on primary fibroblast cell lines from patients with methylmalonic acidemia have delineated a variety of biochemical phenotypes underlying this disorder....

    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.87.8.3147

    authors: Ledley FD,Jansen R,Nham SU,Fenton WA,Rosenberg LE

    更新日期:1990-04-01 00:00:00

  • Changes in solvation during DNA binding and cleavage are critical to altered specificity of the EcoRI endonuclease.

    abstract::Restriction endonucleases such as EcoRI bind and cleave DNA with great specificity and represent a paradigm for protein-DNA interactions and molecular recognition. Using osmotic pressure to induce water release, we demonstrate the participation of bound waters in the sequence discrimination of substrate DNA by EcoRI. ...

    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.95.5.2186

    authors: Robinson CR,Sligar SG

    更新日期:1998-03-03 00:00:00

  • Gene organization of the liverwort Y chromosome reveals distinct sex chromosome evolution in a haploid system.

    abstract::Y chromosomes are different from other chromosomes because of a lack of recombination. Until now, complete sequence information of Y chromosomes has been available only for some primates, although considerable information is available for other organisms, e.g., several species of Drosophila. Here, we report the gene 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.0609054104

    authors: Yamato KT,Ishizaki K,Fujisawa M,Okada S,Nakayama S,Fujishita M,Bando H,Yodoya K,Hayashi K,Bando T,Hasumi A,Nishio T,Sakata R,Yamamoto M,Yamaki A,Kajikawa M,Yamano T,Nishide T,Choi SH,Shimizu-Ueda Y,Hanajiri T,Sa

    更新日期:2007-04-10 00:00:00

  • Ecological character displacement in Plethodon: biomechanical differences found from a geometric morphometric study.

    abstract::Ecological character displacement describes a pattern where morphological differences between sympatric species are enhanced through interspecific competition. Although widely considered a pervasive force in evolutionary ecology, few clear-cut examples have been documented. Here we report a case of ecological characte...

    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.97.8.4106

    authors: Adams DC,Rohlf FJ

    更新日期:2000-04-11 00:00:00

  • Gene-guided discovery and engineering of branched cyclic peptides in plants.

    abstract::The plant kingdom contains vastly untapped natural product chemistry, which has been traditionally explored through the activity-guided approach. Here, we describe a gene-guided approach to discover and engineer a class of plant ribosomal peptides, the branched cyclic lyciumins. Initially isolated from the Chinese wol...

    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.1813993115

    authors: Kersten RD,Weng JK

    更新日期:2018-11-13 00:00:00

  • Global signal of top-down control of terrestrial plant communities by herbivores.

    abstract::The theory of "top-down" ecological regulation predicts that herbivory suppresses plant abundance, biomass, and survival but increases diversity through the disproportionate consumption of dominant species, which inhibits competitive exclusion. To date, these outcomes have been clear in aquatic ecosystems but not on l...

    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.1707984115

    authors: Jia S,Wang X,Yuan Z,Lin F,Ye J,Hao Z,Luskin MS

    更新日期:2018-06-12 00:00:00

  • Viral delivery of glial cell line-derived neurotrophic factor improves behavior and protects striatal neurons in a mouse model of Huntington's disease.

    abstract::Huntington's disease (HD) is a fatal, genetic, neurological disorder resulting from a trinucleotide repeat expansion in the gene that encodes for the protein huntingtin. These excessive repeats confer a toxic gain of function on huntingtin, which leads to the degeneration of striatal and cortical neurons and a devasta...

    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.0508875103

    authors: McBride JL,Ramaswamy S,Gasmi M,Bartus RT,Herzog CD,Brandon EP,Zhou L,Pitzer MR,Berry-Kravis EM,Kordower JH

    更新日期:2006-06-13 00:00:00

  • Gamma-aminobutyrate type B receptor modulation of L-type calcium channel current at bipolar cell terminals in the retina of the tiger salamander.

    abstract::Bipolar-cell axon terminals receive direct synaptic input from amacrine-cell processes, suggesting a possible pathway for modulation of transmitter release. In retinal slices, bath-applied baclofen, a gamma-aminobutyrate type B (GABAB) receptor agonist, reduced a patch-clamp-recorded L-type calcium channel current in ...

    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.86.24.10144

    authors: Maguire G,Maple B,Lukasiewicz P,Werblin F

    更新日期:1989-12-01 00:00:00

  • The visual paired-comparison task as a measure of declarative memory.

    abstract::Performance on the visual paired-comparison task depends on the integrity of the hippocampal formation in humans, monkeys, and, for an analogous task, in rats. The present study sought additional evidence in healthy volunteers concerning the nature of this task. We found that performance on the visual paired-compariso...

    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.220398097

    authors: Manns JR,Stark CE,Squire LR

    更新日期:2000-10-24 00:00:00

  • Pneumococcal carriage results in ganglioside-mediated olfactory tissue infection.

    abstract::Streptococcus pneumoniae cause considerable morbidity and mortality, with persistent neurological sequelae, particularly in young children and the elderly. It is widely assumed that carriage occurs through direct mucosal colonization from the environment whereas meningitis results from invasion from the blood. However...

    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.2235844100

    authors: van Ginkel FW,McGhee JR,Watt JM,Campos-Torres A,Parish LA,Briles DE

    更新日期:2003-11-25 00:00:00

  • Tree-structured supervised learning and the genetics of hypertension.

    abstract::This paper is about an algorithm, FlexTree, for general supervised learning. It extends the binary tree-structured approach (Classification and Regression Trees, CART) although it differs greatly in its selection and combination of predictors. It is particularly applicable to assessing interactions: gene by gene and g...

    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.0403794101

    authors: Huang J,Lin A,Narasimhan B,Quertermous T,Hsiung CA,Ho LT,Grove JS,Olivier M,Ranade K,Risch NJ,Olshen RA

    更新日期:2004-07-20 00:00:00

  • Trans-activation of HLA-DR gene by hepatitis B virus X gene product.

    abstract::Hepatocellular injury during hepatitis B virus (HBV) infection has been postulated to result from a human leukocyte antigen (HLA)-restricted T-lymphocyte host immune response against HBV antigens. Although HLA expression is enhanced in the presence of hepatic inflammation, whether HBV itself can induce HLA expression ...

    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.87.18.7140

    authors: Hu KQ,Vierling JM,Siddiqui A

    更新日期:1990-09-01 00:00:00

  • Serum factors in older individuals change cellular clock properties.

    abstract::Human aging is accompanied by dramatic changes in daily sleep-wake behavior: Activity shifts to an earlier phase, and the consolidation of sleep and wake is disturbed. Although this daily circadian rhythm is brain-controlled, its mechanism is encoded by cell-autonomous circadian clocks functioning in nearly every cell...

    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.1008882108

    authors: Pagani L,Schmitt K,Meier F,Izakovic J,Roemer K,Viola A,Cajochen C,Wirz-Justice A,Brown SA,Eckert A

    更新日期:2011-04-26 00:00:00

  • Topological knots and links in proteins.

    abstract::Twenty years after their discovery, knots in proteins are now quite well understood. They are believed to be functionally advantageous and provide extra stability to protein chains. In this work, we go one step further and search for links-entangled structures, more complex than knots, which consist of several compone...

    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.1615862114

    authors: Dabrowski-Tumanski P,Sulkowska JI

    更新日期:2017-03-28 00:00:00

  • Chromatin proteomic profiling reveals novel proteins associated with histone-marked genomic regions.

    abstract::More than a thousand proteins are thought to contribute to mammalian chromatin and its regulation, but our understanding of the genomic occupancy and function of most of these proteins is limited. Here we describe an approach, which we call "chromatin proteomic profiling," to identify proteins associated with genomic ...

    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.1502971112

    authors: Ji X,Dadon DB,Abraham BJ,Lee TI,Jaenisch R,Bradner JE,Young RA

    更新日期:2015-03-24 00:00:00

  • Position-specific trapping of topoisomerase I-DNA cleavage complexes by intercalated benzo[a]- pyrene diol epoxide adducts at the 6-amino group of adenine.

    abstract::DNA topoisomerase I (top1) is the target of potent anticancer agents, including camptothecins and DNA intercalators, which reversibly stabilize (trap) top1 catalytic intermediates (cleavage complexes). The aim of the present study was to define the structural relationship between the site(s) of covalently bound interc...

    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.190312697

    authors: Pommier Y,Laco GS,Kohlhagen G,Sayer JM,Kroth H,Jerina DM

    更新日期:2000-09-26 00:00:00

  • Nitrofurans, a group of synthetic antibiotics, with a new mode of action: discrimination of specific messenger RNA classes.

    abstract::Nitrofurans, a class of antibacterial drugs in extensive use, interferes with gene expression in a highly specific manner. While in the low dose range (0.5-25 mug/ml), 5-nitro-2-furfurylidene-1-aminohydantoin has no effect on transcription, it inhibits specifically the expression of one class of genes in translation. ...

    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.73.10.3386

    authors: Herrlich P,Schweiger M

    更新日期:1976-10-01 00:00:00

  • TFE and Spt4/5 open and close the RNA polymerase clamp during the transcription cycle.

    abstract::Transcription is an intrinsically dynamic process and requires the coordinated interplay of RNA polymerases (RNAPs) with nucleic acids and transcription factors. Classical structural biology techniques have revealed detailed snapshots of a subset of conformational states of the RNAP as they exist in crystals. A detail...

    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.1515817113

    authors: Schulz S,Gietl A,Smollett K,Tinnefeld P,Werner F,Grohmann D

    更新日期:2016-03-29 00:00:00