rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice.

Abstract:

:Mice carrying mutations in both the dystrophin and utrophin genes die prematurely as a consequence of severe muscular dystrophy. Here, we show that intravascular administration of recombinant adeno-associated viral (rAAV) vectors carrying a microdystrophin gene restores expression of dystrophin in the respiratory, cardiac and limb musculature of these mice, considerably reducing skeletal muscle pathology and extending lifespan. These findings suggest rAAV vector-mediated systemic gene transfer may be useful for treatment of serious neuromuscular disorders such as Duchenne muscular dystrophy.

journal_name

Nat Med

journal_title

Nature medicine

authors

Gregorevic P,Allen JM,Minami E,Blankinship MJ,Haraguchi M,Meuse L,Finn E,Adams ME,Froehner SC,Murry CE,Chamberlain JS

doi

10.1038/nm1439

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

787-9

issue

7

eissn

1078-8956

issn

1546-170X

pii

nm1439

journal_volume

12

pub_type

杂志文章
  • Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization.

    abstract::Retinal neovascularization is a major cause of blindness in such disorders as retinopathy of prematurity, proliferative diabetic retinopathy and senile macular degeneration. Because ligation of vitronectin receptor-type integrins appears to be required for the survival and maturation of newly formed but not quiescent ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0596-529

    authors: Hammes HP,Brownlee M,Jonczyk A,Sutter A,Preissner KT

    更新日期:1996-05-01 00:00:00

  • The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux.

    abstract::Cytochrome P450 3A4 is an important mediator of drug catabolism that can be regulated by the steroid and xenobiotic receptor (SXR). We show here that SXR also regulates drug efflux by activating expression of the gene MDR1, which encodes the protein P-glycoprotein (ABCB1). Paclitaxel (Taxol), a commonly used chemother...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/87912

    authors: Synold TW,Dussault I,Forman BM

    更新日期:2001-05-01 00:00:00

  • Rescue of hearing and vestibular function by antisense oligonucleotides in a mouse model of human deafness.

    abstract::Hearing impairment is the most common sensory disorder, with congenital hearing impairment present in approximately 1 in 1,000 newborns. Hereditary deafness is often mediated by the improper development or degeneration of cochlear hair cells. Until now, it was not known whether such congenital failures could be mitiga...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3106

    authors: Lentz JJ,Jodelka FM,Hinrich AJ,McCaffrey KE,Farris HE,Spalitta MJ,Bazan NG,Duelli DM,Rigo F,Hastings ML

    更新日期:2013-03-01 00:00:00

  • Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma.

    abstract::Whereas uncoupling protein 1 (UCP-1) is clearly involved in thermogenesis, the role of UCP-2 is less clear. Using hybridization, cloning techniques and cDNA array analysis to identify inducible neuroprotective genes, we found that neuronal survival correlates with increased expression of Ucp2. In mice overexpressing h...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm903

    authors: Mattiasson G,Shamloo M,Gido G,Mathi K,Tomasevic G,Yi S,Warden CH,Castilho RF,Melcher T,Gonzalez-Zulueta M,Nikolich K,Wieloch T

    更新日期:2003-08-01 00:00:00

  • Tumor-specific imaging through progression elevated gene-3 promoter-driven gene expression.

    abstract::Molecular-genetic imaging is advancing from a valuable preclinical tool to a guide for patient management. The strategy involves pairing an imaging reporter gene with a complementary imaging agent in a system that can be used to measure gene expression or protein interaction or track gene-tagged cells in vivo. Tissue-...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2269

    authors: Bhang HE,Gabrielson KL,Laterra J,Fisher PB,Pomper MG

    更新日期:2011-01-01 00:00:00

  • Dok1 mediates high-fat diet-induced adipocyte hypertrophy and obesity through modulation of PPAR-gamma phosphorylation.

    abstract::Insulin receptor substrate (IRS)-1 and IRS-2 have dominant roles in the action of insulin, but other substrates of the insulin receptor kinase, such as Gab1, c-Cbl, SH2-B and APS, are also of physiological relevance. Although the protein downstream of tyrosine kinases-1 (Dok1) is known to function as a multisite adapt...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1706

    authors: Hosooka T,Noguchi T,Kotani K,Nakamura T,Sakaue H,Inoue H,Ogawa W,Tobimatsu K,Takazawa K,Sakai M,Matsuki Y,Hiramatsu R,Yasuda T,Lazar MA,Yamanashi Y,Kasuga M

    更新日期:2008-02-01 00:00:00

  • CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma.

    abstract::Although subtypes of pancreatic ductal adenocarcinoma (PDAC) have been described, this malignancy is clinically still treated as a single disease. Here we present patient-derived models representing the full spectrum of previously identified quasi-mesenchymal (QM-PDA), classical and exocrine-like PDAC subtypes, and id...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4038

    authors: Noll EM,Eisen C,Stenzinger A,Espinet E,Muckenhuber A,Klein C,Vogel V,Klaus B,Nadler W,Rösli C,Lutz C,Kulke M,Engelhardt J,Zickgraf FM,Espinosa O,Schlesner M,Jiang X,Kopp-Schneider A,Neuhaus P,Bahra M,Sinn BV,Eil

    更新日期:2016-03-01 00:00:00

  • Mechanisms of NAFLD development and therapeutic strategies.

    abstract::There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosi...

    journal_title:Nature medicine

    pub_type: 杂志文章,评审

    doi:10.1038/s41591-018-0104-9

    authors: Friedman SL,Neuschwander-Tetri BA,Rinella M,Sanyal AJ

    更新日期:2018-07-01 00:00:00

  • VEGF: a modifier of the del22q11 (DiGeorge) syndrome?

    abstract::Hemizygous deletion of chromosome 22q11 (del22q11) causes thymic, parathyroid, craniofacial and life-threatening cardiovascular birth defects in 1 in 4,000 infants. The del22q11 syndrome is likely caused by haploinsufficiency of TBX1, but its variable expressivity indicates the involvement of additional modifiers. Her...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm819

    authors: Stalmans I,Lambrechts D,De Smet F,Jansen S,Wang J,Maity S,Kneer P,von der Ohe M,Swillen A,Maes C,Gewillig M,Molin DG,Hellings P,Boetel T,Haardt M,Compernolle V,Dewerchin M,Plaisance S,Vlietinck R,Emanuel B,Gittenb

    更新日期:2003-02-01 00:00:00

  • A molecularly engineered split reporter for imaging protein-protein interactions with positron emission tomography.

    abstract::Improved techniques to noninvasively image protein-protein interactions (PPIs) are essential. We molecularly engineered a positron emission tomography (PET)-based split reporter (herpes simplex virus type 1 thymidine kinase), cleaved between Thr265 and Ala266, and used this in a protein-fragment complementation assay ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2185

    authors: Massoud TF,Paulmurugan R,Gambhir SS

    更新日期:2010-08-01 00:00:00

  • Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques.

    abstract::The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern: the virus has caused severe respiratory illness, with 111 confirmed cases and 52 deaths at the time of this article's publication. Therapeutic interventions have not been evaluated in vivo; thus, patient management relies ex...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3362

    authors: Falzarano D,de Wit E,Rasmussen AL,Feldmann F,Okumura A,Scott DP,Brining D,Bushmaker T,Martellaro C,Baseler L,Benecke AG,Katze MG,Munster VJ,Feldmann H

    更新日期:2013-10-01 00:00:00

  • Targeting wild-type KRAS-amplified gastroesophageal cancer through combined MEK and SHP2 inhibition.

    abstract::The role of KRAS, when activated through canonical mutations, has been well established in cancer1. Here we explore a secondary means of KRAS activation in cancer: focal high-level amplification of the KRAS gene in the absence of coding mutations. These amplifications occur most commonly in esophageal, gastric and ova...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0022-x

    authors: Wong GS,Zhou J,Liu JB,Wu Z,Xu X,Li T,Xu D,Schumacher SE,Puschhof J,McFarland J,Zou C,Dulak A,Henderson L,Xu P,O'Day E,Rendak R,Liao WL,Cecchi F,Hembrough T,Schwartz S,Szeto C,Rustgi AK,Wong KK,Diehl JA,Jen

    更新日期:2018-07-01 00:00:00

  • Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation.

    abstract::Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation. However, whether inflammation is the cause or the consequence of atrial fibrillation and which specific inflammatory mediators may increase the atria's susceptibility to fibrillation remain el...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2124

    authors: Rudolph V,Andrié RP,Rudolph TK,Friedrichs K,Klinke A,Hirsch-Hoffmann B,Schwoerer AP,Lau D,Fu X,Klingel K,Sydow K,Didié M,Seniuk A,von Leitner EC,Szoecs K,Schrickel JW,Treede H,Wenzel U,Lewalter T,Nickenig G,Zimmer

    更新日期:2010-04-01 00:00:00

  • Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology.

    abstract::Cells from the telomerase knockout mouse immortalize with an approximately ten million-fold greater frequency than human cells. In this commentary, Wright and Shay discuss the implications of this difference between mice and men and its relationship to cancer. ...

    journal_title:Nature medicine

    pub_type: 杂志文章,评审

    doi:10.1038/78592

    authors: Wright WE,Shay JW

    更新日期:2000-08-01 00:00:00

  • Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor.

    abstract::Natural inhibitors of angiogenesis are able to block pathological neovascularization without harming the preexisting vasculature. Here we show that two such inhibitors, thrombospondin-1 and pigment epithelium-derived factor, derive specificity for remodeling vessels from their dependence on Fas/Fas ligand (FasL)-media...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0402-349

    authors: Volpert OV,Zaichuk T,Zhou W,Reiher F,Ferguson TA,Stuart PM,Amin M,Bouck NP

    更新日期:2002-04-01 00:00:00

  • Pro-proliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension.

    abstract::Pulmonary hypertension (PH) is characterized by increased proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs). Forkhead box O (FoxO) transcription factors are key regulators of cellular proliferation. Here we show that in pulmonary vessels and PASMCs of human and experimental PH lun...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3695

    authors: Savai R,Al-Tamari HM,Sedding D,Kojonazarov B,Muecke C,Teske R,Capecchi MR,Weissmann N,Grimminger F,Seeger W,Schermuly RT,Pullamsetti SS

    更新日期:2014-11-01 00:00:00

  • HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures.

    abstract::Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors....

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4292

    authors: Davies H,Glodzik D,Morganella S,Yates LR,Staaf J,Zou X,Ramakrishna M,Martin S,Boyault S,Sieuwerts AM,Simpson PT,King TA,Raine K,Eyfjord JE,Kong G,Borg Å,Birney E,Stunnenberg HG,van de Vijver MJ,Børresen-Dale AL,Ma

    更新日期:2017-04-01 00:00:00

  • Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis.

    abstract::Given the associations between chronic inflammation and epithelial cancer, we studied susceptibility to skin carcinogenesis in mice deficient for the pro-inflammatory cytokine TNF-alpha (refs. 5,6). TNF-alpha(-/-) mice were resistant to development of benign and malignant skin tumors, whether induced by initiation wit...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/10552

    authors: Moore RJ,Owens DM,Stamp G,Arnott C,Burke F,East N,Holdsworth H,Turner L,Rollins B,Pasparakis M,Kollias G,Balkwill F

    更新日期:1999-07-01 00:00:00

  • Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease.

    abstract::Neurofibrillary tangles (NFTs), composed of truncated and hyperphosphorylated tau, are a common feature of numerous aging-related neurodegenerative diseases, including Alzheimer's disease (AD). However, the molecular mechanisms mediating tau truncation and aggregation during aging remain elusive. Here we show that asp...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3700

    authors: Zhang Z,Song M,Liu X,Kang SS,Kwon IS,Duong DM,Seyfried NT,Hu WT,Liu Z,Wang JZ,Cheng L,Sun YE,Yu SP,Levey AI,Ye K

    更新日期:2014-11-01 00:00:00

  • Inducible nitric oxide synthase gene expression in the brain during systemic inflammation.

    abstract::Inducible nitric oxide synthase (iNOS) is a transcriptionally regulated enzyme that synthesizes nitric oxide from L-arginine that has a key role in the pathophysiology of systemic inflammation and sepsis. Transgenic animals with a null mutation for the iNOS gene are resistant to hypotension and death caused by Escheri...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0596-581

    authors: Wong ML,Rettori V,al-Shekhlee A,Bongiorno PB,Canteros G,McCann SM,Gold PW,Licinio J

    更新日期:1996-05-01 00:00:00

  • PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide.

    abstract::Platelet-activating factor (PAF) induces pulmonary edema and has a key role in acute lung injury (ALI). Here we show that PAF induces pulmonary edema through two mechanisms: acid sphingomyelinase (ASM)-dependent production of ceramide, and activation of the cyclooxygenase pathway. Agents that interfere with PAF-induce...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm977

    authors: Göggel R,Winoto-Morbach S,Vielhaber G,Imai Y,Lindner K,Brade L,Brade H,Ehlers S,Slutsky AS,Schütze S,Gulbins E,Uhlig S

    更新日期:2004-02-01 00:00:00

  • Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity.

    abstract::Proper function of the endoplasmic reticulum (ER) and mitochondria is crucial for cellular homeostasis, and dysfunction at either site has been linked to pathophysiological states, including metabolic diseases. Although the ER and mitochondria play distinct cellular roles, these organelles also form physical interacti...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3735

    authors: Arruda AP,Pers BM,Parlakgül G,Güney E,Inouye K,Hotamisligil GS

    更新日期:2014-12-01 00:00:00

  • Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB.

    abstract::Programmed cell death (apoptosis) seems to be the principal mechanism whereby anti-oncogenic therapies such as chemotherapy and radiation effect their responses. Resistance to apoptosis, therefore, is probably a principal mechanism whereby tumors are able to overcome these cancer therapies. The transcription factor NF...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/7410

    authors: Wang CY,Cusack JC Jr,Liu R,Baldwin AS Jr

    更新日期:1999-04-01 00:00:00

  • Active movement of T cells away from a chemokine.

    abstract::Movement towards or away from a given stimulus guides the directional migration of prokaryotes, simple eukaryotes and neurons. As bi-directional cues may influence entry and exit of immune effector cells from tissue sites, we evaluated the migratory responses of T-cell subsets to varying concentrations of the chemokin...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/75022

    authors: Poznansky MC,Olszak IT,Foxall R,Evans RH,Luster AD,Scadden DT

    更新日期:2000-05-01 00:00:00

  • Selective changes in single cell GABA(A) receptor subunit expression and function in temporal lobe epilepsy.

    abstract::Temporal lobe epilepsy is the most prevalent seizure disorder in adults. Compromised inhibitory neurotransmitter function in the hippocampus contributes to the hyperexcitability generating this condition, but the underlying molecular mechanisms are unknown. Combining patch-clamp recording and single-cell mRNA amplific...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/2661

    authors: Brooks-Kayal AR,Shumate MD,Jin H,Rikhter TY,Coulter DA

    更新日期:1998-10-01 00:00:00

  • Differential requirement for CD18 in T-helper effector homing.

    abstract::To understand the integrin requirements of T-helper (T(H)) effector subsets, we investigated the contribution of CD18 (beta(2) integrin) to T(H)1 and T(H)2 function in vitro and in relevant disease models. CD18-deficient (Itgb2(-/-)) T cells showed largely normal in vitro function. Compared with wild-type mice, Itgb2(...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm932

    authors: Lee SH,Prince JE,Rais M,Kheradmand F,Shardonofsky F,Lu H,Beaudet AL,Smith CW,Soong L,Corry DB

    更新日期:2003-10-01 00:00:00

  • Bovine beta-lactoglobulin modified by 3-hydroxyphthalic anhydride blocks the CD4 cell receptor for HIV.

    abstract::Sexual transmission is the most frequent (86%) route of adult HIV-1 transmission worldwide. In the absence of a prophylactic anti-HIV vaccine, other methods of preventing infection should be implemented. Virucidal spermicides have been considered for this purpose, but their application is contraindicated by adverse ef...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0296-230

    authors: Neurath AR,Jiang S,Strick N,Lin K,Li YY,Debnath AK

    更新日期:1996-02-01 00:00:00

  • Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington's disease.

    abstract::Huntington's disease (HD) is a fatal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion leading to an elongated polyglutamine stretch in huntingtin. Mutant huntingtin (mHTT) is ubiquitously expressed in all cells but elicits selective cortical and striatal neurodegeneration in HD. The mec...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3514

    authors: Wang N,Gray M,Lu XH,Cantle JP,Holley SM,Greiner E,Gu X,Shirasaki D,Cepeda C,Li Y,Dong H,Levine MS,Yang XW

    更新日期:2014-05-01 00:00:00

  • Immunity or tolerance: opposite outcomes of microchimerism from skin grafts.

    abstract::Solid organ transplants contain small numbers of leukocytes that can migrate into the host and establish long-lasting microchimerism. Although such microchimerism is often associated with graft acceptance and tolerance, it has been difficult to demonstrate a true causal link. Using skin from mutant mice deficient for ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/83393

    authors: Anderson CC,Matzinger P

    更新日期:2001-01-01 00:00:00

  • Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke.

    abstract::Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme gamma-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apopto...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1403

    authors: Arumugam TV,Chan SL,Jo DG,Yilmaz G,Tang SC,Cheng A,Gleichmann M,Okun E,Dixit VD,Chigurupati S,Mughal MR,Ouyang X,Miele L,Magnus T,Poosala S,Granger DN,Mattson MP

    更新日期:2006-06-01 00:00:00