Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model.

Abstract:

:Duchenne muscular dystrophy (DMD) is the most common and lethal genetic muscle disorder, caused by recessive mutations in the dystrophin gene. One of every 3,500 males suffers from DMD, yet no treatment is currently available. Genetic therapeutic approaches, using primarily myoblast transplantation and adenovirus-mediated gene transfer, have met with limited success. Adeno-associated virus (AAV) vectors, although proven superior for muscle gene transfer, are too small (5 kb) to package the 14-kb dystrophin cDNA. Here we have created a series of minidystrophin genes (<4.2 kb) under the control of a muscle-specific promoter that readily package into AAV vectors. When injected into the muscle of mdx mice (a DMD model), two of the minigenes resulted in efficient and stable expression in a majority of the myofibers, restoring the missing dystrophin and dystrophin-associated protein complexes onto the plasma membrane. More importantly, this AAV treatment ameliorated dystrophic pathology in mdx muscle and led to normal myofiber morphology, histology, and cell membrane integrity. Thus, we have defined minimal functional dystrophin units and demonstrated the effectiveness of using AAV to deliver the minigenes in vivo, offering a promising avenue for DMD gene therapy.

authors

Wang B,Li J,Xiao X

doi

10.1073/pnas.240335297

keywords:

subject

Has Abstract

pub_date

2000-12-05 00:00:00

pages

13714-9

issue

25

eissn

0027-8424

issn

1091-6490

pii

240335297

journal_volume

97

pub_type

杂志文章
  • Investigations into the relationship between structure and function of diphtheria toxin.

    abstract::Studies on the structure-function relationship of diphtheria toxin are reported. New methods are described for the preparation of pure intact ("unnicked") toxin and for the preparation of the individual A and B chains. A biological assay method for the B chain is also presented, as well as a method for the labelling 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.74.2.472

    authors: Everse J,Lappi DA,Beglau JM,Lee CL,Kaplan NO

    更新日期:1977-02-01 00:00:00

  • Folding of human superoxide dismutase: disulfide reduction prevents dimerization and produces marginally stable monomers.

    abstract::The molecular mechanism by which the homodimeric enzyme Cu/Zn superoxide dismutase (SOD) causes neural damage in amytrophic lateral sclerosis is yet poorly understood. A striking, as well as an unusual, feature of SOD is that it maintains intrasubunit disulfide bonds in the reducing environment of the cytosol. Here, w...

    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.0403979101

    authors: Lindberg MJ,Normark J,Holmgren A,Oliveberg M

    更新日期:2004-11-09 00:00:00

  • Mechanical properties of sensory hair bundles are reflected in their Brownian motion measured with a laser differential interferometer.

    abstract::By optically probing with a focused, low-power laser beam, we measured the spontaneous deflection fluctuations of the sensory hair bundles on frog saccular hair cells with a sensitivity of about 1 pm/square root of Hz. The preparation was illuminated by two orthogonally polarized laser beams separated by only about 0....

    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.86.14.5371

    authors: Denk W,Webb WW,Hudspeth AJ

    更新日期:1989-07-01 00:00:00

  • Strategy for reversing resistance to a single anticancer agent in human prostate and pancreatic carcinomas.

    abstract::Effective therapies for most solid cancers, especially those that have progressed to metastasis, remain elusive because of inherent and acquired resistance of tumor cells to conventional treatments. Additionally, the effective therapeutic window for many protocols can be very narrow, frequently resulting in toxicity. ...

    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.0700042104

    authors: Lebedeva IV,Washington I,Sarkar D,Clark JA,Fine RL,Dent P,Curiel DT,Turro NJ,Fisher PB

    更新日期:2007-02-27 00:00:00

  • Critical role of soluble amyloid-β for early hippocampal hyperactivity in a mouse model of Alzheimer's disease.

    abstract::Alzheimer's disease (AD) is characterized by a progressive dysfunction of central neurons. Recent experimental evidence indicates that in the cortex, in addition to the silencing of a fraction of neurons, other neurons are hyperactive in amyloid-β (Aβ) plaque-enriched regions. However, it has remained unknown what com...

    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.1206171109

    authors: Busche MA,Chen X,Henning HA,Reichwald J,Staufenbiel M,Sakmann B,Konnerth A

    更新日期:2012-05-29 00:00:00

  • Analysis of human tumors and human malignant cell lines for BK virus-specific DNA sequences.

    abstract::Most humans in the United States have been infected with BK virus (BKV), a human papovavirus. Because BKV has oncogenic properties, we have investigated whether it may be a cause of human cancer. Basic principles of tumor virology imply that BKV-induced tumors should contain BKV DNA sequences. Therefore, we assayed (b...

    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.75.1.454

    authors: Wold WS,Mackey JK,Brackmann KH,Takemori N,Rigden P,Green M

    更新日期:1978-01-01 00:00:00

  • Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain.

    abstract::Helicobacter pylori VacA, a pore-forming toxin secreted by an autotransporter pathway, causes multiple alterations in human cells, contributes to the pathogenesis of peptic ulcer disease and gastric cancer, and is a candidate antigen for inclusion in an H. pylori vaccine. Here, we present a 2.4-A crystal structure of ...

    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.0707447104

    authors: Gangwer KA,Mushrush DJ,Stauff DL,Spiller B,McClain MS,Cover TL,Lacy DB

    更新日期:2007-10-09 00:00:00

  • Evolution of compensatory substitutions through G.U intermediate state in Drosophila rRNA.

    abstract::It has often been suggested that the frequently observed Watson-Crick base-pair compensatory substitutions in RNA helical structures occur mainly through a slightly deleterious G.U intermediate state. We have scored base substitutions in a set of 82 related Drosophila species for the D1 and D2 variable domains 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.88.22.10032

    authors: Rousset F,Pélandakis M,Solignac M

    更新日期:1991-11-15 00:00:00

  • Chromosomal radiosensitivity during the G2 cell-cycle period of skin fibroblasts from individuals with familial cancer.

    abstract::We reported previously that human cells after neoplastic transformation in culture had acquired an increased susceptibility to chromatid damage induced by x-irradiation during the G2 phase of the cell cycle. Evidence suggested that this results from deficient DNA repair during G2 phase. Cells derived from human tumors...

    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.82.16.5400

    authors: Parshad R,Sanford KK,Jones GM

    更新日期:1985-08-01 00:00:00

  • Interaction between the GAGA factor and Mod(mdg4) proteins promotes insulator bypass in Drosophila.

    abstract::Chromatin insulators or boundaries are proposed to structure the chromatin fiber into functionally independent domains by promoting the formation of chromatin loops. These elements can block the communication between an enhancer and a gene when placed between them. Interestingly, it has been previously observed that t...

    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.0403959101

    authors: Melnikova L,Juge F,Gruzdeva N,Mazur A,Cavalli G,Georgiev P

    更新日期:2004-10-12 00:00:00

  • Auxin inhibits stomatal development through MONOPTEROS repression of a mobile peptide gene STOMAGEN in mesophyll.

    abstract::Plants, as sessile organisms, must coordinate various physiological processes to adapt to ever-changing surrounding environments. Stomata, the epidermal pores facilitating gas and water exchange, play important roles in optimizing photosynthetic efficiency and adaptability. Stomatal development is under the control of...

    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.1400542111

    authors: Zhang JY,He SB,Li L,Yang HQ

    更新日期:2014-07-22 00:00:00

  • Energy-transducing thylakoid membranes remain highly impermeable to ions during protein translocation.

    abstract::We investigated the operation of a posttranslational protein translocation pathway to determine whether ions are excluded from the translocase during protein transport. The membrane capacitance during protein translocation across chloroplast thylakoid membranes was monitored via electric-field-indicating carotenoid el...

    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.95.4.1590

    authors: Teter SA,Theg SM

    更新日期:1998-02-17 00:00:00

  • The N-terminal 22 amino acid residues in the lactose permease of Escherichia coli are not obligatory for membrane insertion or transport activity.

    abstract::When the lactose (lac) permease of Escherichia coli is expressed from the lac promoter at relatively low rates, deletion of amino acid residues 2-8 (delta 7) or 2-9 (delta 8) from the hydrophilic N terminus has a relatively minor effect on the ability of the permease to catalyze active lactose transport. Activity is e...

    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.89.8.3180

    authors: Bibi E,Stearns SM,Kaback HR

    更新日期:1992-04-15 00:00:00

  • Androgen insensitivity in man: evidence for genetic heterogeneity.

    abstract::We have studied ten phenotypically similar patients with complete androgen insensitivity. All of the patients tested had significantly elevated serum luteinizing hormone and plasma androgens within or above the normal adult male range. On the basis of specific dihydrotestosterone binding by skin fibroblasts, we identi...

    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.73.3.891

    authors: Amrhein JA,Meyer WJ 3rd,Jones HW Jr,Migeon CJ

    更新日期:1976-03-01 00:00:00

  • Acuity-independent effects of visual deprivation on human visual cortex.

    abstract::Visual development depends on sensory input during an early developmental critical period. Deviation of the pointing direction of the two eyes (strabismus) or chronic optical blur (anisometropia) separately and together can disrupt the formation of normal binocular interactions and the development of spatial processin...

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

    pub_type: 杂志文章,随机对照试验

    doi:10.1073/pnas.1404361111

    authors: Hou C,Pettet MW,Norcia AM

    更新日期:2014-07-29 00:00:00

  • Supervillin associates with androgen receptor and modulates its transcriptional activity.

    abstract::Activation of androgen receptor (AR) via androgen in muscle cells has been closely linked to their growth and differentiation. Here, we report the cloning and characterization of supervillin (SV), a 205-kDa actin-binding protein, as an AR coregulator from the skeletal muscle cDNA library. Mammalian two-hybrid and glut...

    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.022469899

    authors: Ting HJ,Yeh S,Nishimura K,Chang C

    更新日期:2002-01-22 00:00:00

  • Evolution of resistance to satyrization through reproductive character displacement in populations of invasive dengue vectors.

    abstract::Recently, the highly invasive Asian tiger mosquito, Aedes albopictus, rapidly displaced resident populations of the yellow fever mosquito, Aedes aegypti in the southeastern United States and in Bermuda. Although multiple mechanisms of competitive displacement have been hypothesized, recent evidence of cross-inseminati...

    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.1219599110

    authors: Bargielowski IE,Lounibos LP,Carrasquilla MC

    更新日期:2013-02-19 00:00:00

  • Evolutionary changes of multiple visual pigment genes in the complete genome of Pacific bluefin tuna.

    abstract::Tunas are migratory fishes in offshore habitats and top predators with unique features. Despite their ecological importance and high market values, the open-ocean lifestyle of tuna, in which effective sensing systems such as color vision are required for capture of prey, has been poorly understood. To elucidate the ge...

    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.1302051110

    authors: Nakamura Y,Mori K,Saitoh K,Oshima K,Mekuchi M,Sugaya T,Shigenobu Y,Ojima N,Muta S,Fujiwara A,Yasuike M,Oohara I,Hirakawa H,Chowdhury VS,Kobayashi T,Nakajima K,Sano M,Wada T,Tashiro K,Ikeo K,Hattori M,Kuhara S,

    更新日期:2013-07-02 00:00:00

  • A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1.

    abstract::Tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) by the insulin receptor permits this docking protein to interact with signaling proteins that promote insulin action. Serine phosphorylation uncouples IRS-1 from the insulin receptor, thereby inhibiting its tyrosine phosphorylation and insulin signaling....

    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.051042298

    authors: Ozes ON,Akca H,Mayo LD,Gustin JA,Maehama T,Dixon JE,Donner DB

    更新日期:2001-04-10 00:00:00

  • High-temperature environments of human evolution in East Africa based on bond ordering in paleosol carbonates.

    abstract::Many important hominid-bearing fossil localities in East Africa are in regions that are extremely hot and dry. Although humans are well adapted to such conditions, it has been inferred that East African environments were cooler or more wooded during the Pliocene and Pleistocene when this region was a central stage of ...

    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.1001824107

    authors: Passey BH,Levin NE,Cerling TE,Brown FH,Eiler JM

    更新日期:2010-06-22 00:00:00

  • A glycoprotein associated with the non-A, non-B hepatitis agent(s): isolation and immunoreactivity.

    abstract::A glycoprotein was isolated and purified to homogeneity from the serum of a patient with chronic non-A, non-B hepatitis. NaDodSO4/PAGE of the glycoprotein revealed a single major band at Mr approximately 77,000. Antibodies to this glycoprotein were shown to possess the following immunoreactivity: (i) they reacted by r...

    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.82.15.4934

    authors: Seto B,Gerety RJ

    更新日期:1985-08-01 00:00:00

  • Proteins of Escherichia coli come in sizes that are multiples of 14 kDa: domain concepts and evolutionary implications.

    abstract::Initial attempts to correlate the distribution of gene density (number of gene loci per unit length on the linkage map) with the distribution of lengths of coding sequences have led to the observation that 46% of approximately 1000 sampled proteins in Escherichia coli have molecular masses of n X 14,000 +/- 2500 dalto...

    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.83.5.1198

    authors: Savageau MA

    更新日期:1986-03-01 00:00:00

  • Roles of glutamates and metal ions in a rationally designed nitric oxide reductase based on myoglobin.

    abstract::A structural and functional model of bacterial nitric oxide reductase (NOR) has been designed by introducing two glutamates (Glu) and three histidines (His) in sperm whale myoglobin. X-ray structural data indicate that the three His and one Glu (V68E) residues bind iron, mimicking the putative Fe(B) site in NOR, while...

    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.1000526107

    authors: Lin YW,Yeung N,Gao YG,Miner KD,Tian S,Robinson H,Lu Y

    更新日期:2010-05-11 00:00:00

  • Use of a monoclonal antibody to purify the tetrodotoxin binding component from the electroplax of Electrophorus electricus.

    abstract::The tetrodotoxin binding component of the voltage-sensitive sodium channel from Electrophorus electricus electroplax was purified by using a monoclonal antibody. An impure preparation of tetrodotoxin binding component was mixed with the pure monoclonal antibody, and the immune complex so formed was isolated by affinit...

    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.79.23.7575

    authors: Nakayama H,Withy RM,Raftery MA

    更新日期:1982-12-01 00:00:00

  • The adaptor protein APPL2 controls glucose-stimulated insulin secretion via F-actin remodeling in pancreatic β-cells.

    abstract::Filamentous actin (F-actin) cytoskeletal remodeling is critical for glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells, and its dysregulation causes type 2 diabetes. The adaptor protein APPL1 promotes first-phase GSIS by up-regulating soluble N-ethylmaleimide-sensitive factor attachment protein receptor...

    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.2016997117

    authors: Wang B,Lin H,Li X,Lu W,Kim JB,Xu A,Cheng KKY

    更新日期:2020-11-10 00:00:00

  • Notch pathway regulation of chondrocyte differentiation and proliferation during appendicular and axial skeleton development.

    abstract::The role of Notch signaling in cartilage differentiation and maturation in vivo was examined. Conditional Notch pathway gain and loss of function was achieved using a Cre/loxP approach to manipulate Notch signaling in cartilage precursors and chondrocytes of the developing mouse embryo. Conditional overexpression of a...

    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.0902306106

    authors: Mead TJ,Yutzey KE

    更新日期:2009-08-25 00:00:00

  • Transcription initiation is controlled by three core promoter elements in the hgl5 gene of the protozoan parasite Entamoeba histolytica.

    abstract::Entamoeba histolytica is a single cell eukaryote that is the etiologic agent of amoebic colitis. Core promoter elements of E. histolytica protein encoding genes include a TATA-like sequence (GTATTTAAAG/C) at -30, a novel element designated GAAC (GAACT) that has a variable location between TATA and the site of transcri...

    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.94.16.8812

    authors: Singh U,Rogers JB,Mann BJ,Petri WA Jr

    更新日期:1997-08-05 00:00:00

  • Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain.

    abstract::Phenotypic modification of dorsal root ganglion (DRG) neurons represents an important mechanism underlying neuropathic pain. However, the nerve injury-induced molecular changes are not fully identified. To determine the molecular alterations in a broader way, we have carried out cDNA array on the genes mainly made fro...

    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.122231899

    authors: Xiao HS,Huang QH,Zhang FX,Bao L,Lu YJ,Guo C,Yang L,Huang WJ,Fu G,Xu SH,Cheng XP,Yan Q,Zhu ZD,Zhang X,Chen Z,Han ZG,Zhang X

    更新日期:2002-06-11 00:00:00

  • Geoelectric potential changes: possible precursors to earthquakes in Japan.

    abstract::Whether electromagnetic precursors to earthquakes (EQs) exist is an important question not only for EQ prediction but also for understanding the physical processes of EQ generation. Slow transient geoelectric potential changes have been observed before several recent EQs in Japan. In most cases, they appeared 1-19 day...

    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.97.9.4561

    authors: Uyeda S,Nagao T,Orihara Y,Yamaguchi T,Takahashi I

    更新日期:2000-04-25 00:00:00

  • Anti-viral protection conferred by recombinant adenylate cyclase toxins from Bordetella pertussis carrying a CD8+ T cell epitope from lymphocytic choriomeningitis virus.

    abstract::The elucidation of the mechanisms of antigen presentation by major histocompatibility complex class I molecules has stimulated the search for nonreplicative vectors that could deliver CD8+ T cell epitopes to the cytosol of antigen-presenting cells to trigger the activation of specific cytotoxic T lymphocytes (CTLs) 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.94.7.3314

    authors: Saron MF,Fayolle C,Sebo P,Ladant D,Ullmann A,Leclerc C

    更新日期:1997-04-01 00:00:00