当前位置： SCI文献检索 > Molecular Therapy-Methods & Clinical Development期刊下所有文献 > Genetically Corrected iPSC-Derived Neural Stem Cell Grafts Deliver Enzyme Replacement to Affect CNS Disease in Sanfilippo B Mice.

Genetically Corrected iPSC-Derived Neural Stem Cell Grafts Deliver Enzyme Replacement to Affect CNS Disease in Sanfilippo B Mice.

Abstract：

:Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB [MPS IIIB]) is a lysosomal storage disorder primarily affecting the brain that is caused by a deficiency in the enzyme α-N-acetylglucosaminidase (NAGLU), leading to intralysosomal accumulation of heparan sulfate. There are currently no treatments for this disorder. Here we report that, ex vivo, lentiviral correction of Naglu -/- neural stem cells derived from Naglu -/- mice (iNSCs) corrected their lysosomal pathology and allowed them to secrete a functional NAGLU enzyme that could be taken up by deficient cells. Following long-term transplantation of these corrected iNSCs into Naglu -/- mice, we detected NAGLU activity in the majority of engrafted animals. Successfully transplanted Naglu -/- mice showed a significant decrease in storage material, a reduction in astrocyte activation, and complete prevention of microglial activation within the area of engrafted cells and neighboring regions, with beneficial effects extending partway along the rostrocaudal axis of the brain. Our results demonstrate long-term engraftment of iNSCs in the brain that are capable of cross-correcting pathology in Naglu -/- mice. Our findings suggest that genetically engineered iNSCs could potentially be used to deliver enzymes and treat MPS IIIB.

journal_name

Mol Ther Methods Clin Dev

journal_title

Molecular therapy. Methods & clinical development

authors

Clarke D,Pearse Y,Kan SH,Le SQ,Sanghez V,Cooper JD,Dickson PI,Iacovino M

doi

10.1016/j.omtm.2018.06.005

subject

Has Abstract

pub_date

2018-07-23 00:00:00

pages

113-127

issn

2329-0501

pii

S2329-0501(18)30059-7

journal_volume

10

pub_type

杂志文章

相关文献

Molecular Therapy-Methods & Clinical Development文献大全
  • 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

  • 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

  • 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

  • A qPCR Method for AAV Genome Titer with ddPCR-Level of Accuracy and Precision.

    abstract：:Recombinant adeno-associated virus (rAAV) is one of the main vectors used in gene therapy. An accurate genome titer is not only critical for clinical dosing, but also a prerequisite for many analytical assays for AAV product characterization. AAV genome titer is traditionally determined by qPCR; however, assay precisi...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2020.09.017

    authors： Wang Y,Menon N,Shen S,Feschenko M,Bergelson S

    更新日期：2020-10-01 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • Transient Chimeric Ad5/37 Fiber Enhances NK-92 Carrier Cell-Mediated Delivery of Oncolytic Adenovirus Type 5 to Tumor Cells.

    abstract：:Methods for customizing and improving virus vector tropism are limited. In this study, we introduce a microRNA (miRNA)-regulated molecular method to enhance vector transduction without genome alteration. Based on the importance of adenovirus (Ad) vectors for cancer and gene treatment, we exemplified this technology fo...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2020.06.010

    authors： Gao J,Zhang W,Mese K,Bunz O,Lu F,Ehrhardt A

    更新日期：2020-06-18 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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 mur...

    journal_title：Molecular therapy. Methods & clinical development

    pub_type： 杂志文章

    doi：10.1016/j.omtm.2018.03.002

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

    更新日期：2018-03-10 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

  • 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

  • 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

  • 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