当前位置： SCI文献检索 > Molecular Therapy-Methods & Clinical Development期刊下所有文献 > Preclinical Development of a Lentiviral Vector for Gene Therapy of X-Linked Severe Combined Immunodeficiency.

Preclinical Development of a Lentiviral Vector for Gene Therapy of X-Linked Severe Combined Immunodeficiency.

Abstract：

:X-linked severe combined immunodeficiency (SCID-X1) is caused by mutations in the interleukin-2 receptor γ chain gene (IL2RG), and it is characterized by profound defects in T, B, and natural killer (NK) cell functions. Transplantation of hematopoietic stem/progenitor cells (HSPCs) genetically corrected with early murine leukemia retrovirus (MLV)-derived gammaretroviral vectors showed restoration of T cell immunity in patients, but it resulted in vector-induced insertional oncogenesis. We developed a self-inactivating (SIN) lentiviral vector carrying a codon-optimized human IL2RG cDNA driven by the EF1α short promoter (EFS-IL2RG), and we tested its efficacy and safety in vivo by transplanting transduced Il2rg-deficient Lin- HSPCs in an Il2rg-/-/Rag2-/- mouse model. The study showed restoration of T, B, and NK cell counts in bone marrow and peripheral blood and normalization of thymus and spleen cellularity and architecture. High-definition insertion site analysis defined the EFS-IL2RG genomic integration profile, and it showed no sign of vector-induced clonal selection or skewing in primarily and secondarily transplanted animals. The study enables a phase I/II clinical trial aimed at restoring both T and B cell immunity in SCID-X1 children upon non-myeloablative conditioning.

journal_name

Mol Ther Methods Clin Dev

journal_title

Molecular therapy. Methods & clinical development

authors

Poletti V,Charrier S,Corre G,Gjata B,Vignaud A,Zhang F,Rothe M,Schambach A,Gaspar HB,Thrasher AJ,Mavilio F

doi

10.1016/j.omtm.2018.03.002

subject

Has Abstract

pub_date

2018-03-10 00:00:00

pages

257-269

issn

2329-0501

pii

S2329-0501(18)30026-3

journal_volume

9

pub_type

杂志文章

相关文献

Molecular Therapy-Methods & Clinical Development文献大全
  • piggyBac-mediated phenotypic correction of factor VIII deficiency.

    abstract：:Hemophilia A, caused by a deficiency in factor VIII (FVIII), is the most severe inherited bleeding disorder. Hemophilia A is an attractive gene therapy candidate because even small increases in FVIII levels will positively alter the phenotype. While several vectors are under investigation, gene addition from an integr...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2014.42

    authors： Staber JM,Pollpeter MJ,Arensdorf A,Sinn PL,Rutkowski DT,McCray PB Jr

    更新日期：2014-09-10 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

  • Analyzing the Genotoxicity of Retroviral Vectors in Hematopoietic Cell Gene Therapy.

    abstract：:Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章,评审

    doi：10.1016/j.omtm.2017.10.002

    authors： Biasco L,Rothe M,Büning H,Schambach A

    更新日期：2017-10-05 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

  • All-in-one processing of heterogeneous human cell grafts for gene and cell therapy.

    abstract：:Current cell processing technologies for gene and cell therapies are often slow, expensive, labor intensive and are compromised by high cell losses and poor selectivity thus limiting the efficacy and availability of clinical cell therapies. We employ cell-specific on-demand mechanical intracellular impact from laser p...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2016.12

    authors： Lukianova-Hleb EY,Yvon ES,Shpall EJ,Lapotko DO

    更新日期：2016-03-16 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • High-throughput monitoring of integration site clonality in preclinical and clinical gene therapy studies.

    abstract：:Gene transfer to hematopoietic stem cells with integrating vectors not only allows sustained correction of monogenic diseases but also tracking of individual clones in vivo. Quantitative real-time PCR (qPCR) has been shown to be an accurate method to quantify individual stem cell clones, yet due to frequently limited ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2014.61

    authors： Giordano FA,Appelt JU,Link B,Gerdes S,Lehrer C,Scholz S,Paruzynski A,Roeder I,Wenz F,Glimm H,von Kalle C,Grez M,Schmidt M,Laufs S

    更新日期：2015-04-01 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

  • 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

  • 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

  • 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

  • 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 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

  • 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 ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2019.12.002

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

    更新日期：2019-12-14 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

  • 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

  • rAAVrh74.MCK.GALGT2 Demonstrates Safety and Widespread Muscle Glycosylation after Intravenous Delivery in C57BL/6J Mice.

    abstract：:rAAVrh74.MCK.GALGT2 is a surrogate gene therapy that inhibits muscular dystrophy in multiple animal models. Here, we report on a dose-response study of functional muscle GALGT2 expression as well as toxicity and biodistribution studies after systemic intravenous (i.v.) delivery of rAAVrh74.MCK.GALGT2. A dose of 4.3 × ...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2019.10.005

    authors： Zygmunt DA,Xu R,Jia Y,Ashbrook A,Menke C,Shao G,Yoon JH,Hamilton S,Pisharath H,Bolon B,Martin PT

    更新日期：2019-10-21 00:00:00

  • Treatment of osteoarthritis using a helper-dependent adenoviral vector retargeted to chondrocytes.

    abstract：:Osteoarthritis (OA) is a joint disease characterized by degeneration of the articular cartilage, subchondral bone remodeling, and secondary inflammation. It is among the top three causes of chronic disability, and currently there are no treatment options to prevent disease progression. The localized nature of OA makes...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1038/mtm.2016.8

    authors： Ruan MZ,Cerullo V,Cela R,Clarke C,Lundgren-Akerlund E,Barry MA,Lee BH

    更新日期：2016-03-09 00:00:00

  • Transduction Pattern of AAVs in the Trabecular Meshwork and Anterior-Segment Structures in a Rat Model of Ocular Hypertension.

    abstract：:Adeno-associated viruses (AAVs) are the vector of choice for gene therapy in the eye, and self-complementary AAVs (scAAVs), which do not require second-strand DNA synthesis, can be transduced into cells of the trabecular meshwork (TM). The scAAV transduction patterns in the anterior segment of normotensive eyes have b...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2019.06.009

    authors： Lee SH,Sim KS,Kim CY,Park TK

    更新日期：2019-07-10 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

  • 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

  • Defining the Optimal FVIII Transgene for Placental Cell-Based Gene Therapy to Treat Hemophilia A.

    abstract：:The delivery of factor VIII (FVIII) through gene and/or cellular platforms has emerged as a promising hemophilia A treatment. Herein, we investigated the suitability of human placental cells (PLCs) as delivery vehicles for FVIII and determined an optimal FVIII transgene to produce/secrete therapeutic FVIII levels from...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2020.03.001

    authors： El-Akabawy N,Rodriguez M,Ramamurthy R,Rabah A,Trevisan B,Morsi A,George S,Shields J,Meares D,Farland A,Atala A,Doering CB,Spencer HT,Porada CD,Almeida-Porada G

    更新日期：2020-03-14 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

  • 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

  • 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