当前位置： SCI文献检索 > Molecular Therapy-Methods & Clinical Development期刊下所有文献 > A comparison of AAV strategies distinguishes overlapping vectors for efficient systemic delivery of the 6.2 kb Dysferlin coding sequence.

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, overlapping vectors, hybrid dual or fragmented AAV). Loss of function mutations in the DYSF gene whose coding sequence is 6.2kb lead to progressive muscular dystrophies (LGMD2B: OMIM_253601; MM: OMIM_254130; DMAT: OMIM_606768). In this study, we compared large gene transfer techniques to deliver the DYSF gene into the skeletal muscle. After rAAV8s intramuscular injection into dysferlin deficient mice, we showed that the overlap strategy is the most effective approach to reconstitute a full-length messenger. After systemic administration, the level of dysferlin obtained on different muscles corresponded to 0.5- to 2-fold compared to the normal level. We further demonstrated that the overlapping vector set was efficient to correct the histopathology, resistance to eccentric contractions and whole body force in the dysferlin deficient mice. Altogether, these data indicate that using overlapping vectors could be a promising approach for a potential clinical treatment of dysferlinopathies.

journal_name

Mol Ther Methods Clin Dev

journal_title

Molecular therapy. Methods & clinical development

authors

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

doi

10.1038/mtm.2015.9

subject

Has Abstract

pub_date

2015-03-25 00:00:00

pages

15009

issn

2329-0501

pii

S2329-0501(16)30021-3

journal_volume

2

pub_type

杂志文章

相关文献

Molecular Therapy-Methods & Clinical Development文献大全
  • Establishment of SLC15A1/PEPT1-Knockout Human-Induced Pluripotent Stem Cell Line for Intestinal Drug Absorption Studies.

    abstract：:Because many peptide and peptide-mimetic drugs are substrates of peptide transporter 1, it is important to evaluate the peptide transporter 1-mediated intestinal absorption of drug candidates in the early phase of drug development. Although intestinal cell lines treated with inhibitors of peptide transporter 1 are wid...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2019.11.008

    authors： Kawai K,Negoro R,Ichikawa M,Yamashita T,Deguchi S,Harada K,Hirata K,Takayama K,Mizuguchi H

    更新日期：2019-11-21 00:00:00

  • A Nontoxic Transduction Enhancer Enables Highly Efficient Lentiviral Transduction of Primary Murine T Cells and Hematopoietic Stem Cells.

    abstract：:Lentiviral vectors have emerged as an efficient, safe therapeutic tool for gene therapy based on hematopoietic stem cells (HSCs) or T cells. However, the monitoring of transduced cells in preclinical models remains challenging because of the inefficient transduction of murine primary T cells with lentiviral vectors, i...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2018.08.002

    authors： Delville M,Soheili T,Bellier F,Durand A,Denis A,Lagresle-Peyrou C,Cavazzana M,Andre-Schmutz I,Six E

    更新日期：2018-08-08 00:00:00

  • 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

  • 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 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

  • 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

  • A Robust System for Production of Superabundant VP1 Recombinant AAV Vectors.

    abstract：:Recombinant adeno-associated viral (rAAV) vectors have been widely used in human gene therapy. One major impediment to its broad application is the inability to produce high-quality vectors in mass quantity. Here, an efficient and scalable suspension cell culture system for the production of rAAV vectors is described....

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2017.11.002

    authors： Wang Q,Wu Z,Zhang J,Firrman J,Wei H,Zhuang Z,Liu L,Miao L,Hu Y,Li D,Diao Y,Xiao W

    更新日期：2017-11-07 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

  • Translational Feasibility of Lumbar Puncture for Intrathecal AAV Administration.

    abstract：:Preclinical studies have demonstrated that a single injection of an adeno-associated virus (AAV) vector into the cerebrospinal fluid (CSF) can achieve widespread gene transfer throughout the central nervous system. Successfully translating this approach to humans requires identifying factors that influence AAV distrib...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2020.04.012

    authors： Hinderer C,Katz N,Dyer C,Goode T,Johansson J,Bell P,Richman L,Buza E,Wilson JM

    更新日期：2020-04-18 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

  • Lentiviral Hematopoietic Stem Cell Gene Therapy Corrects Murine Pompe Disease.

    abstract：:Pompe disease is an autosomal recessive lysosomal storage disorder characterized by progressive muscle weakness. The disease is caused by mutations in the acid α-glucosidase (GAA) gene. Despite the currently available enzyme replacement therapy (ERT), roughly half of the infants with Pompe disease die before the age o...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2020.04.023

    authors： Stok M,de Boer H,Huston MW,Jacobs EH,Roovers O,Visser TP,Jahr H,Duncker DJ,van Deel ED,Reuser AJJ,van Til NP,Wagemaker G

    更新日期：2020-05-04 00:00:00

  • EPPIC (Efficient Purification by Parental Inducer Constraint) Platform for Rapid Generation of Recombinant Vaccinia Viruses.

    abstract：:Vaccinia virus (VACV) was successfully used as a vaccine in the smallpox eradication campaign. Since then, it has been widely used in the development of vaccine and therapeutic vectors. However, methods of generating and purifying recombinant VACVs (rVACVs) are often time-consuming, cumbersome, and in some cases requi...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2020.03.026

    authors： Jasperse B,O'Connell CM,Wang Y,Verardi PH

    更新日期：2020-03-30 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

  • 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

  • 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

  • Development of Gene Transfer for Induction of Antigen-specific Tolerance.

    abstract：:Gene replacement therapies, like organ and cell transplantation are likely to introduce neo-antigens that elicit rejection via humoral and/or effector T cell immune responses. Nonetheless, thanks to an ever growing body of pre-clinical studies it is now well accepted that gene transfer protocols can be specifically de...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2014.13

    authors： Sack BK,Herzog RW,Terhorst C,Markusic DM

    更新日期：2014-04-30 00:00:00

  • RD-MolPack technology for the constitutive production of self-inactivating lentiviral vectors pseudotyped with the nontoxic RD114-TR envelope.

    abstract：:To date, gene therapy with transiently derived lentivectors has been very successful to cure rare infant genetic diseases. However, transient manufacturing is unfeasible to treat adult malignancies because large vector lots are required. By contrast, stable manufacturing is the best option for high-incidence diseases ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2016.33

    authors： Marin V,Stornaiuolo A,Piovan C,Corna S,Bossi S,Pema M,Giuliani E,Scavullo C,Zucchelli E,Bordignon C,Rizzardi GP,Bovolenta C

    更新日期：2016-05-11 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

  • 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

  • Removal of Endotoxin from rAAV Samples Using a Simple Detergent-Based Protocol.

    abstract：:Endotoxin is the most common contaminant found in protein samples. Even a small amount of endotoxin can induce strong allergic reaction and death of a host organism. Endotoxin is also often detected in recombinant adeno-associated virus (rAAV) stocks prepared in research laboratories using off-the-shelf reagents; puri...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2019.08.013

    authors： Kondratova L,Kondratov O,Ragheb R,Zolotukhin S

    更新日期：2019-09-06 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

  • Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic.

    abstract：:Rituximab is a mouse/human chimeric monoclonal antibody targeted toward CD20. It is efficient as first-line therapy of CD20-positive B-cell malignancies. However, a large fraction of treated patients relapse with rituximab-resistant disease. So far, only modest progress has been made in treatment options for rituximab...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2016.13

    authors： Richter M,Yumul R,Saydaminova K,Wang H,Gough M,Baldessari A,Cattaneo R,Lee F,Wang CH,Jang H,Astier A,Gopal A,Carter D,Lieber A

    更新日期：2016-03-30 00:00:00

  • Amelioration of Muscle and Nerve Pathology in LAMA2 Muscular Dystrophy by AAV9-Mini-Agrin.

    abstract：:LAMA2-related muscular dystrophy (LAMA2 MD) is the most common and fatal form of early-onset congenital muscular dystrophies. Due to the large size of the laminin α2 cDNA and heterotrimeric structure of the protein, it is challenging to develop a gene-replacement therapy. Our group has developed a novel adeno-associat...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2018.01.005

    authors： Qiao C,Dai Y,Nikolova VD,Jin Q,Li J,Xiao B,Li J,Moy SS,Xiao X

    更新日期：2018-01-31 00:00:00

  • Dynamics of antigen presentation to transgene product-specific CD4+ T cells and of Treg induction upon hepatic AAV gene transfer.

    abstract：:The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in viral vector gene transfer, which often results in immune tolerance induction to transgene products. Although the underlying tolerance mechanism has been extensively studied, our understanding of antigen presentation ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2016.83

    authors： Perrin GQ,Zolotukhin I,Sherman A,Biswas M,de Jong YP,Terhorst C,Davidoff AM,Herzog RW

    更新日期：2016-12-07 00:00:00

  • Plastin 3 Promotes Motor Neuron Axonal Growth and Extends Survival in a Mouse Model of Spinal Muscular Atrophy.

    abstract：:Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease. SMA is caused by mutations in the survival motor neuron gene (SMN1), leading to reduced levels of SMN protein in the CNS. The actin-binding protein plastin 3 (PLS3) has been reported as a modifier for SMA, making it a potential therapeutic ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2018.01.007

    authors： Alrafiah A,Karyka E,Coldicott I,Iremonger K,Lewis KE,Ning K,Azzouz M

    更新日期：2018-01-31 00:00:00

  • The Use of Values WNR and GNR to Distinguish between and Diagnose Different Types of Pancreatitis.

    abstract：:There is no effective serologic parameter to distinguish different types of pancreatitis now. To distinguish between acute pancreatitis (AP) and acute exacerbations of chronic pancreatitis (CP) and to determine whether fibrosis occurs in CP, we evaluated the ability to produce white blood cells (WBCs), the neutrophil-...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2020.05.010

    authors： Luo L,Zhang J,Yang J,Zhang H,Tang Y,Yang D,Dong H,Wu Y,Wang H,Ni B,Tian Z

    更新日期：2020-05-22 00:00:00

  • Corrigendum to "Efficient gene delivery to photoreceptors using AAV2/rh10 and rescue of the Rho-/- mouse".

    abstract：:[This corrects the article DOI: 10.1038/mtm.2015.16.]. ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 已发布勘误

    doi：10.1038/mtm.2016.32

    authors： Palfi A,Chadderton N,O'Reilly M,Nagel-Wolfrum K,Wolfrum U,Bennett J,Humphries P,Kenna P,Millington-Ward S,Farrar J

    更新日期：2016-05-25 00:00:00

  • Generation and in vivo evaluation of IL10-treated dendritic cells in a nonhuman primate model of AAV-based gene transfer.

    abstract：:Preventing untoward immune responses against a specific antigen is a major challenge in different clinical settings such as gene therapy, transplantation, or autoimmunity. Following intramuscular delivery of recombinant adeno-associated virus (rAAV)-derived vectors, transgene rejection can be a roadblock to successful...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2014.28

    authors： Moreau A,Vandamme C,Segovia M,Devaux M,Guilbaud M,Tilly G,Jaulin N,Le Duff J,Cherel Y,Deschamps JY,Anegon I,Moullier P,Cuturi MC,Adjali O

    更新日期：2014-07-23 00:00:00

  • Treatment of Hypertensive Heart Disease by Targeting Smad3 Signaling in Mice.

    abstract：:Transforming growth factor β (TGF-β)/Smad3 signaling plays a central role in chronic heart disease. Here, we report that targeting Smad3 with a Smad3 inhibitor SIS3 in an established mouse model of hypertension significantly improved cardiac dysfunctions by preserving the left ventricle (LV) ejection fraction (LVEF) a...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2020.08.003

    authors： Meng J,Qin Y,Chen J,Wei L,Huang XR,Yu X,Lan HY

    更新日期：2020-08-05 00:00:00

  • Determining the Minimally Effective Dose of a Clinical Candidate AAV Vector in a Mouse Model of Crigler-Najjar Syndrome.

    abstract：:Liver metabolism disorders are attractive targets for gene therapy, because low vector doses can reverse the buildup of toxic metabolites in the blood. Crigler-Najjar syndrome is an inherited disorder of bilirubin metabolism that is caused by the absence of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) act...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2018.07.008

    authors： Greig JA,Nordin JML,Draper C,McMenamin D,Chroscinski EA,Bell P,Gray JT,Richman LK,Wilson JM

    更新日期：2018-07-21 00:00:00