当前位置： SCI文献检索 > Molecular Therapy-Methods & Clinical Development期刊下所有文献 > Urocortin 2 Gene Transfer Improves Glycemic Control and Reduces Retinopathy and Mortality in Murine Insulin Deficiency.

Urocortin 2 Gene Transfer Improves Glycemic Control and Reduces Retinopathy and Mortality in Murine Insulin Deficiency.

Abstract：

:Type 1 diabetes affects 20 million patients worldwide. Insulin is the primary and commonly the sole therapy for type 1 diabetes. However, only a minority of patients attain the targeted glucose control and reduced adverse events. We tested urocortin 2 gene transfer as single-agent therapy for insulin deficiency using two mouse models. Urocortin 2 gene transfer reduced blood glucose for months after a single intravenous injection, through increased skeletal muscle insulin sensitivity, increased insulin release in response to glucose stimulation, and increased plasma insulin levels before and during euglycemic clamp. The combined increases in both insulin availability and sensitivity resulted in improved glycemic indices-events that were not anticipated in these insulin-deficient models. In addition, urocortin 2 gene transfer reduced ocular manifestations of long-standing insulin deficiency such as vascular leak and improved retinal function. Finally, mortality was reduced by urocortin 2 gene transfer. The mechanisms for these beneficial effects included increased activities of AMP-activated protein kinase and Akt (protein kinase B) in skeletal muscle, increased skeletal muscle glucose uptake, and increased insulin release. These data suggest that urocortin 2 gene transfer may be a viable therapy for new onset type 1 diabetes and might reduce insulin needs in later stage disease.

journal_name

Mol Ther Methods Clin Dev

journal_title

Molecular therapy. Methods & clinical development

authors

Gao MH,Giamouridis D,Lai NC,Guo T,Xia B,Kim YC,Huu VAN,Skowronska-Krawczyk D,Lantier L,Bhargava R,Hammond HK

doi

10.1016/j.omtm.2019.12.002

subject

Has Abstract

pub_date

2019-12-14 00:00:00

pages

220-233

issn

2329-0501

pii

S2329-0501(19)30148-2

journal_volume

17

pub_type

杂志文章

相关文献

Molecular Therapy-Methods & Clinical Development文献大全
  • Development of a real-time imaging system for hypoxic cell apoptosis.

    abstract：:Hypoxic regions within the tumor form due to imbalances between cell proliferation and angiogenesis; specifically, temporary closure or a reduced flow due to abnormal vasculature. They create environments where cancer cells acquire resistance to therapies. Therefore, the development of therapeutic approaches targeting...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2016.9

    authors： Kagiya G,Ogawa R,Hyodo F,Yamashita K,Nakamura M,Ishii A,Sejimo Y,Tominaga S,Murata M,Tanaka Y,Hatashita M

    更新日期：2016-03-02 00:00:00

  • A translationally optimized AAV-UGT1A1 vector drives safe and long-lasting correction of Crigler-Najjar syndrome.

    abstract：:Crigler-Najjar syndrome is a severe metabolic disease of the liver due to a reduced activity of the UDP Glucuronosyltransferase 1A1 (UGT1A1) enzyme. In an effort to translate to the clinic an adeno-associated virus vector mediated liver gene transfer approach to treat Crigler-Najjar syndrome, we developed and optimize...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2016.49

    authors： Ronzitti G,Bortolussi G,van Dijk R,Collaud F,Charles S,Leborgne C,Vidal P,Martin S,Gjata B,Sola MS,van Wittenberghe L,Vignaud A,Veron P,Bosma PJ,Muro AF,Mingozzi F

    更新日期：2016-07-20 00:00:00

  • Treatment of hypophosphatasia by muscle-directed expression of bone-targeted alkaline phosphatase via self-complementary AAV8 vector.

    abstract：:Hypophosphatasia (HPP) is an inherited disease caused by genetic mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNALP). This results in defects in bone and tooth mineralization. We recently demonstrated that TNALP-deficient (Akp2 (-/-) ) mice, which mimic the phenotype of the severe infantile ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2015.59

    authors： Nakamura-Takahashi A,Miyake K,Watanabe A,Hirai Y,Iijima O,Miyake N,Adachi K,Nitahara-Kasahara Y,Kinoshita H,Noguchi T,Abe S,Narisawa S,Millán JL,Shimada T,Okada T

    更新日期：2016-02-03 00:00:00

  • Membrane-stabilizing copolymers confer marked protection to dystrophic skeletal muscle in vivo.

    abstract：:Duchenne muscular dystrophy (DMD) is a fatal disease of striated muscle deterioration. A unique therapeutic approach for DMD is the use of synthetic membrane stabilizers to protect the fragile dystrophic sarcolemma against contraction-induced mechanical stress. Block copolymer-based membrane stabilizer poloxamer 188 (...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2015.42

    authors： Houang EM,Haman KJ,Filareto A,Perlingeiro RC,Bates FS,Lowe DA,Metzger JM

    更新日期：2015-11-11 00:00:00

  • DNAJC14 Ameliorates Inner Ear Degeneration in the DFNB4 Mouse Model.

    abstract：:The His723Arg (H723R) mutation in SLC26A4, encoding pendrin, is the most prevalent mutation in East Asia, resulting in DFNB4, an autosomal recessive type of genetic hearing loss. Although the main pathological mechanism of H723R was identified as a protein-folding defect in pendrin, there is still no curative treatmen...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2019.11.019

    authors： Choi HJ,Lee HJ,Choi JY,Jeon IH,Noh B,Devkota S,Lee HW,Eo SK,Choi JY,Lee MG,Jung J

    更新日期：2019-11-30 00:00:00

  • AAV8 Gene Therapy for Crigler-Najjar Syndrome in Macaques Elicited Transgene T Cell Responses That Are Resident to the Liver.

    abstract：:Systemic delivery of adeno-associated viral (AAV) vectors has been evaluated for the treatment of several liver diseases, including homozygous familial hypercholesterolemia, ornithine transcarbamylase deficiency, and hemophilia. Here, we evaluated this approach for the treatment of Crigler-Najjar syndrome. We administ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2018.10.012

    authors： Greig JA,Calcedo R,Kuri-Cervantes L,Nordin JML,Albrecht J,Bote E,Goode T,Chroscinski EA,Bell P,Richman LK,Betts MR,Wilson JM

    更新日期：2018-12-05 00:00:00

  • Conditionally Replicating Vectors Mobilize Chimeric Antigen Receptors against HIV.

    abstract：:Human immunodeficiency virus (HIV) is an attractive target for chimeric antigen receptor (CAR) therapy. CAR T cells have proved remarkably potent in targeted killing of cancer cells, and we surmised that CAR T cells could prove useful in eradicating HIV-infected cells. Toward this goal, we interrogate several neutrali...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2020.09.014

    authors： Urak RZ,Soemardy C,Ray R,Li S,Shevchenko G,Scott T,Lim L,Wang X,Morris KV

    更新日期：2020-09-28 00:00:00

  • Partial Reconstruction of the Nigrostriatal Circuit along a Preformed Molecular Guidance Pathway.

    abstract：:The overall goal of our research is to establish a preformed molecular guidance pathway to direct the growth of dopaminergic axons from embryonic ventral mesencephalon (VM), tissue placed within the substantia nigra (SN), into the striatum to reconstruct the nigrostriatal pathway in a hemi-Parkinson's disease rat mode...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2019.06.008

    authors： Ghosh B,Zhang C,Ziemba KS,Fletcher AM,Yurek DM,Smith GM

    更新日期：2019-07-11 00:00:00

  • Single AAV-Mediated CRISPR-SaCas9 Inhibits HSV-1 Replication by Editing ICP4 in Trigeminal Ganglion Neurons.

    abstract：:Herpes simplex keratitis (HSK) is the most common cause of corneal blindness in developed nations, caused by primary or recurrent herpes simplex virus 1 (HSV-1) infection of the cornea. Latent infection of HSV-1, especially in the trigeminal ganglion (TG), causes recurrence of HSV-1 infection. As antiviral treatment i...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2020.05.011

    authors： Chen Y,Zhi S,Liang P,Zheng Q,Liu M,Zhao Q,Ren J,Cui J,Huang J,Liu Y,Songyang Z

    更新日期：2020-05-22 00:00:00

  • Quantitative, noninvasive, in vivo longitudinal monitoring of gene expression in the brain by co-AAV transduction with a PET reporter gene.

    abstract：:In vivo imaging of vector transgene expression would be particularly valuable for repetitive monitoring of therapy in the brain, where invasive tissue sampling is contraindicated. We evaluated adeno-associated virus vector expression of a dopamine-2 receptor (D2R) mutant (D2R80A) by positron emission tomography in the...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2014.16

    authors： Yoon SY,Gay-Antaki C,Ponde DE,Poptani H,Vite CH,Wolfe JH

    更新日期：2014-06-04 00:00:00

  • Immunoresponse to Gene-Modified Hematopoietic Stem Cells.

    abstract：:Gene transfer to and correction of hematopoietic stem cells (HSCs) are ideal strategies to cure a number of congenital and acquired disorders. However, transgene products may trigger immunological rejection of modified cells, limiting their therapeutic benefits. Preclinical and clinical data indicate that myeloablativ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章,评审

    doi：10.1016/j.omtm.2019.10.010

    authors： Drysdale CM,Tisdale JF,Uchida N

    更新日期：2019-10-31 00:00:00

  • Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease.

    abstract：:We present an overview of clinical trials involving gene editing using clustered interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), or zinc finger nucleases (ZFNs) and discuss the underlying mechanisms. In cancer immunotherapy, g...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章,评审

    doi：10.1016/j.omtm.2020.06.022

    authors： Ernst MPT,Broeders M,Herrero-Hernandez P,Oussoren E,van der Ploeg AT,Pijnappel WWMP

    更新日期：2020-07-03 00:00:00

  • A Generic Assay to Detect Aberrant ARSB Splicing and mRNA Degradation for the Molecular Diagnosis of MPS VI.

    abstract：:Identification and characterization of disease-associated variants in monogenic disorders is an important aspect of diagnosis, genetic counseling, prediction of disease severity, and development of therapy. However, the effects of disease-associated variants on pre-mRNA splicing and mRNA degradation are difficult to p...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2020.09.004

    authors： Broeders M,Smits K,Goynuk B,Oussoren E,van den Hout HJMP,Bergsma AJ,van der Ploeg AT,Pijnappel WWMP

    更新日期：2020-09-16 00:00:00

  • Genetic barcode sequencing for screening altered population dynamics of hematopoietic stem cells transduced with lentivirus.

    abstract：:Insertional mutagenesis has been associated with malignant cell transformation in gene therapy protocols, leading to discussions about vector security. Therefore, clonal analysis is important for the assessment of vector safety and its impact on patient health. Here, we report a unique approach to assess dynamic chang...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2014.52

    authors： Zanatta DB,Tsujita M,Borelli P,Aguiar RB,Ferrari DG,Strauss BE

    更新日期：2014-11-19 00:00:00

  • Toward a Rapid Production of Multivirus-Specific T Cells Targeting BKV, Adenovirus, CMV, and EBV from Umbilical Cord Blood.

    abstract：:Umbilical cord blood (CB) has emerged as an effective alternative donor source for hematopoietic stem cell transplantation. Despite this success, the prolonged duration of immune suppression following CB transplantation and the naiveté of CB T cells leave patients susceptible to viral infections. Adoptive transfer of ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2017.02.001

    authors： Dave H,Luo M,Blaney JW,Patel S,Barese C,Cruz CR,Shpall EJ,Bollard CM,Hanley PJ

    更新日期：2017-03-08 00:00:00

  • Syngeneic AAV Pseudo-particles Potentiate Gene Transduction of AAV Vectors.

    abstract：:Adeno-associated virus (AAV) vectors have emerged as a safe and efficient gene therapy platform. One complication is that a significant amount of empty particles have always been generated as impurities during AAV vector production. However, the effects of such particles on AAV vector performance remain unclear. Here ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2016.12.004

    authors： Wang Q,Dong B,Pokiniewski KA,Firrman J,Wu Z,Chin MP,Chen X,Liu L,Xu R,Diao Y,Xiao W

    更新日期：2016-12-24 00:00:00

  • Human Umbilical Tissue-Derived Cells Secrete Soluble VEGFR1 and Inhibit Choroidal Neovascularization.

    abstract：:Exudative age-related macular degeneration (AMD), characterized by choroidal neovascularization (CNV), is the leading cause of irreversible blindness in developed countries. Anti-vascular endothelial growth factor (VEGF) drugs are the standard treatment for AMD, but they have limitations. Cell therapy is a promising a...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2019.05.007

    authors： Cao J,Yang R,Smith TE,Evans S,McCollum GW,Pomerantz SC,Petley T,Harris IR,Penn JS

    更新日期：2019-05-22 00:00:00

  • MTBVAC-Based TB-HIV Vaccine Is Safe, Elicits HIV-T Cell Responses, and Protects against Mycobacterium tuberculosis in Mice.

    abstract：:The tuberculosis (TB) vaccine MTBVAC is the only live-attenuated Mycobacterium tuberculosis (Mtb)-based vaccine in clinical development, and it confers superior protection in different animal models compared to the current vaccine, BCG (Mycobacterium bovis bacillus Calmette-Guérin). With the aim of using MTBVAC as a v...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2019.01.014

    authors： Broset E,Saubi N,Guitart N,Aguilo N,Uranga S,Kilpeläinen A,Eto Y,Hanke T,Gonzalo-Asensio J,Martín C,Joseph-Munné J

    更新日期：2019-02-07 00:00:00

  • INSPIIRED: A Pipeline for Quantitative Analysis of Sites of New DNA Integration in Cellular Genomes.

    abstract：:Integration of new DNA into cellular genomes mediates replication of retroviruses and transposons; integration reactions have also been adapted for use in human gene therapy. Tracking the distributions of integration sites is important to characterize populations of transduced cells and to monitor potential outgrow of...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2016.11.002

    authors： Sherman E,Nobles C,Berry CC,Six E,Wu Y,Dryga A,Malani N,Male F,Reddy S,Bailey A,Bittinger K,Everett JK,Caccavelli L,Drake MJ,Bates P,Hacein-Bey-Abina S,Cavazzana M,Bushman FD

    更新日期：2016-12-18 00:00:00

  • TFEB overexpression promotes glycogen clearance of Pompe disease iPSC-derived skeletal muscle.

    abstract：:Pompe disease (PD) is a lysosomal disorder caused by acid α-glucosidase (GAA) deficiency. Progressive muscular weakness is the major symptom of PD, and enzyme replacement therapy can improve the clinical outcome. However, to achieve a better clinical outcome, alternative therapeutic strategies are being investigated, ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2016.54

    authors： Sato Y,Kobayashi H,Higuchi T,Shimada Y,Ida H,Ohashi T

    更新日期：2016-08-10 00:00:00

  • Codon-Optimization of Wild-Type Adeno-Associated Virus Capsid Sequences Enhances DNA Family Shuffling while Conserving Functionality.

    abstract：:Adeno-associated virus (AAV) vectors have become one of the most widely used gene transfer tools in human gene therapy. Considerable effort is currently being focused on AAV capsid engineering strategies with the aim of developing novel variants with enhanced tropism for specific human cell types, decreased human sero...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2018.10.016

    authors： Cabanes-Creus M,Ginn SL,Amaya AK,Liao SHY,Westhaus A,Hallwirth CV,Wilmott P,Ward J,Dilworth KL,Santilli G,Rybicki A,Nakai H,Thrasher AJ,Filip AC,Alexander IE,Lisowski L

    更新日期：2018-11-01 00:00:00

  • Liposome Lipid-Based Formulation Has the Least Influence on rAAV Transduction Compared to Other Transfection Agents.

    abstract：:Recombinant adeno-associated virus (rAAV) vectors are considered ideal vehicles for human gene therapy. Meanwhile, non-viral strategies, such as transfection agents (TAs), have also shown promise to deliver genetic materials, such as siRNA. Transduction with the rAAV vector is performed concurrently with transfection ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2018.04.004

    authors： Guo P,Yu C,Wang Q,Zhang R,Meng X,Feng Y

    更新日期：2018-04-12 00:00:00

  • A human surfactant B deficiency air-liquid interface cell culture model suitable for gene therapy applications.

    abstract：:Surfactant protein B (SPB) deficiency is a severe monogenic interstitial lung disorder that leads to loss of life in infants as a result of alveolar collapse and respiratory distress syndrome. The development and assessment of curative therapies for the deficiency are limited by the general lack of well-characterized ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2020.11.013

    authors： Munis AM,Hyde SC,Gill DR

    更新日期：2020-11-20 00:00:00

  • Human fetal liver cells for regulated ex vivo erythropoietin gene therapy.

    abstract：:Possible risks and lack of donor livers limit application of liver transplantation. Liver cell transplantation is, at this moment, not a feasible alternative because engraftment in the liver is poor. Furthermore, there is also shortage of cells suitable for transplantation. Fetal liver cells are able to proliferate in...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2014.3

    authors： El Filali E,Duijst S,Hiralall JK,Legrand N,van Gulik T,Hoekstra R,Seppen J

    更新日期：2014-03-12 00:00:00

  • An Isolated Limb Infusion Method Allows for Broad Distribution of rAAVrh74.MCK.GALGT2 to Leg Skeletal Muscles in the Rhesus Macaque.

    abstract：:Recombinant adeno-associated virus (rAAV)rh74.MCK.GALGT2 is a muscle-specific gene therapy that is being developed to treat forms of muscular dystrophy. Here we report on an isolated limb infusion technique in a non-human primate model, where hindlimb blood flow is transiently isolated using balloon catheters to conce...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2018.06.002

    authors： Xu R,Jia Y,Zygmunt DA,Cramer ML,Crowe KE,Shao G,Maki AE,Guggenheim HN,Hood BC,Griffin DA,Peterson E,Bolon B,Cheatham JP,Cheatham SL,Flanigan KM,Rodino-Klapac LR,Chicoine LG,Martin PT

    更新日期：2018-07-14 00:00:00

  • Clodronate Improves Survival of Transplanted Hoxb8 Myeloid Progenitors with Constitutively Active GMCSFR in Immunocompetent Mice.

    abstract：:New methods to produce large numbers of myeloid progenitor cells, precursors to macrophages (MΦs), by maintaining Hoxb8 transcription factor activity1 has reinvigorated interest in MΦ cell therapies. We generated Hoxb8-dependent myeloid progenitors (HDPs) by transducing lineage-negative bone marrow cells with a consti...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2017.08.007

    authors： Lee S,Kivimäe S,Szoka FC

    更新日期：2017-09-07 00:00:00

  • Genetic Engineering and Manufacturing of Hematopoietic Stem Cells.

    abstract：:The marketing approval of genetically engineered hematopoietic stem cells (HSCs) as the first-line therapy for the treatment of severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID) is a tribute to the substantial progress that has been made regarding HSC engineering in the past decade. Rep...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章,评审

    doi：10.1016/j.omtm.2017.03.003

    authors： Wang X,Rivière I

    更新日期：2017-03-18 00:00:00

  • A comparison of AAV strategies distinguishes overlapping vectors for efficient systemic delivery of the 6.2 kb Dysferlin coding sequence.

    abstract：:Recombinant adeno-associated virus (rAAV) is currently the best vector for gene delivery into the skeletal muscle. However, the 5-kb packaging size of this virus is a major obstacle for large gene transfer. This past decade, many different strategies were developed to circumvent this issue (concatemerization-splicing,...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2015.9

    authors： Pryadkina M,Lostal W,Bourg N,Charton K,Roudaut C,Hirsch ML,Richard I

    更新日期：2015-03-25 00:00:00

  • CRISPR Activation Enhances In Vitro Potency of AAV Vectors Driven by Tissue-Specific Promoters.

    abstract：:Validation of gene transfer vectors containing tissue-specific promoters in cell-based functional assays poses a formidable challenge for gene therapy product development. Here, we describe a novel approach based on CRISPR/dCas9 transcriptional activation to achieve robust transgene expression from transgene cassettes...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2019.03.004

    authors： McDougald DS,Duong TT,Palozola KC,Marsh A,Papp TE,Mills JA,Zhou S,Bennett J

    更新日期：2019-03-28 00:00:00

  • Cre Recombinase Mediates the Removal of Bacterial Backbone to Efficiently Generate rSV40.

    abstract：:Gene therapy has been shown to be a feasible approach to treat inherited disorders in vivo. Among the currently used viral vector systems, adeno-associated virus (AAV) vectors are the most advanced and have been applied in patients successfully. An important drawback of non-integrating AAV vectors is their loss of exp...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2018.02.010

    authors： Shi X,Ykema MR,Hazenoot J,Ten Bloemendaal L,Mancini I,Odijk M,de Haan P,Bosma PJ

    更新日期：2018-02-27 00:00:00