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  1. AU="Le Duff, Johanne"
  2. AU="Mutsvangwa, T"
  3. AU="Dowsey, Andrew W."
  4. AU="López-Méndez, Rosalía"
  5. AU="Maisano, Valerio"
  6. AU="Chen, Du"
  7. AU="Thomas J. LaSalle"
  8. AU=Misra Lopa
  9. AU="Rachel P. L. van Swelm"
  10. AU=Sheik Amamuddy Olivier
  11. AU="Régis Resende Paulinelli"
  12. AU=Saxon Jamie A.
  13. AU="Jarvis, Casey M"
  14. AU="Karki, Sudesha"
  15. AU="Caregnato-Neto, Angelo"
  16. AU=Iwakura Katsuomi
  17. AU="Lin, Shengyun"
  18. AU=Huang Jun
  19. AU="Leng, Jiancai"
  20. AU="Rutgers van der Loeff, Michiel M"
  21. AU="Penak, Bianca"
  22. AU="Shao, Shiliang"
  23. AU="Haro-Barceló, Júlia"
  24. AU="Jian Zeng"
  25. AU="Toyoda, Masanori"
  26. AU=Levine Ross L
  27. AU="Michael N. Antoniou"
  28. AU="Mushtaq, Rabeea"
  29. AU="Elwany Elsnosy"
  30. AU="Bertilacchi, Maria Sofia"
  31. AU="I.C.F.Wong, "
  32. AU="Pootrakul, Llana"
  33. AU="Heydari Beni, Nargess"
  34. AU="Pinter, Emily N"
  35. AU="Hogan, William J"
  36. AU="Tikute, Sanjaykumar"
  37. AU="Lu Shi"
  38. AU="A.Allocca, "
  39. AU="Collinge, Mark"
  40. AU="Fullaondo, Asier"
  41. AU="Yang, Jingrui"

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  1. Artikel ; Online: Prevalence Study of Cellular Capsid-Specific Immune Responses to AAV2, 4, 5, 8, 9, and rh10 in Healthy Donors.

    Xicluna, Rebecca / Avenel, Allan / Vandamme, Céline / Devaux, Marie / Jaulin, Nicolas / Couzinié, Célia / Le Duff, Johanne / Charrier, Alicia / Guilbaud, Mickaël / Adjali, Oumeya / Gernoux, Gwladys

    Human gene therapy

    2024  

    Abstract: Recombinant adeno-associated virus (rAAV) vectors appear, more than ever, to be efficient viral vectors ... ...

    Abstract Recombinant adeno-associated virus (rAAV) vectors appear, more than ever, to be efficient viral vectors for
    Sprache Englisch
    Erscheinungsdatum 2024-04-19
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 1028152-6
    ISSN 1557-7422 ; 1043-0342
    ISSN (online) 1557-7422
    ISSN 1043-0342
    DOI 10.1089/hum.2023.225
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  2. Artikel: AAV8 locoregional delivery induces long-term expression of an immunogenic transgene in macaques despite persisting local inflammation.

    Gernoux, Gwladys / Guilbaud, Mickaël / Devaux, Marie / Journou, Malo / Pichard, Virginie / Jaulin, Nicolas / Léger, Adrien / Le Duff, Johanne / Deschamps, Jack-Yves / Le Guiner, Caroline / Moullier, Philippe / Cherel, Yan / Adjali, Oumeya

    Molecular therapy. Methods & clinical development

    2021  Band 20, Seite(n) 660–674

    Abstract: Adeno-associated virus (AAV) vectors are considered efficient vectors for gene transfer, as illustrated by recent successful clinical trials targeting retinal or neurodegenerative disorders. However, limitations as host immune responses to AAV capsid or ... ...

    Abstract Adeno-associated virus (AAV) vectors are considered efficient vectors for gene transfer, as illustrated by recent successful clinical trials targeting retinal or neurodegenerative disorders. However, limitations as host immune responses to AAV capsid or transduction of limited regions must still be overcome. Here, we focused on locoregional (LR) intravenous perfusion vector delivery that allows transduction of large muscular areas and is considered to be less immunogenic than intramuscular (IM) injection. To confirm this hypothesis, we injected 6 cynomolgus monkeys with an AAV serotype 8 (AAV8) vector encoding for the highly immunogenic GFP driven by either a muscle-specific promoter (n = 3) or a cytomegalovirus (CMV) promoter (n = 3). We report that LR delivery allows long-term GFP expression in the perfused limb (up to 1 year) despite the initiation of a peripheral transgene-specific immune response. The analysis of the immune status of the perfused limb shows that LR delivery induces persisting inflammation. However, this inflammation is not sufficient to result in transgene clearance and is balanced by resident regulatory T cells. Overall, our results suggest that LR delivery promotes persisting transgene expression by induction of Treg cells
    Sprache Englisch
    Erscheinungsdatum 2021-02-06
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2872938-9
    ISSN 2329-0501 ; 2329-0501
    ISSN (online) 2329-0501
    ISSN 2329-0501
    DOI 10.1016/j.omtm.2021.02.003
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Tetramer-Based Enrichment of Preexisting Anti-AAV8 CD8

    Vandamme, Céline / Xicluna, Rebecca / Hesnard, Leslie / Devaux, Marie / Jaulin, Nicolas / Guilbaud, Mickaël / Le Duff, Johanne / Couzinié, Célia / Moullier, Philippe / Saulquin, Xavier / Adjali, Oumeya

    Frontiers in immunology

    2020  Band 10, Seite(n) 3110

    Abstract: Pre-existing immunity to AAV capsid may compromise the safety and efficiency of rAAV-mediated gene transfer in patients. Anti-capsid cytotoxic immune responses have proven to be a challenge to characterize because of the scarcity of circulating AAV- ... ...

    Abstract Pre-existing immunity to AAV capsid may compromise the safety and efficiency of rAAV-mediated gene transfer in patients. Anti-capsid cytotoxic immune responses have proven to be a challenge to characterize because of the scarcity of circulating AAV-specific CD8
    Mesh-Begriff(e) Adult ; Aged ; CD8-Positive T-Lymphocytes/immunology ; Capsid Proteins/genetics ; Capsid Proteins/immunology ; Dependovirus/genetics ; Dependovirus/immunology ; Female ; Genetic Therapy/instrumentation ; Genetic Vectors/genetics ; Genetic Vectors/immunology ; Humans ; Immunologic Memory ; Interferon-gamma/genetics ; Interferon-gamma/immunology ; Male ; Middle Aged ; Receptors, CCR7/genetics ; Receptors, CCR7/immunology ; Young Adult
    Chemische Substanzen CCR7 protein, human ; Capsid Proteins ; Receptors, CCR7 ; Interferon-gamma (82115-62-6)
    Sprache Englisch
    Erscheinungsdatum 2020-01-21
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2019.03110
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Five Years of Successful Inducible Transgene Expression Following Locoregional Adeno-Associated Virus Delivery in Nonhuman Primates with No Detectable Immunity.

    Guilbaud, Mickaël / Devaux, Marie / Couzinié, Celia / Le Duff, Johanne / Toromanoff, Alice / Vandamme, Céline / Jaulin, Nicolas / Gernoux, Gwladys / Larcher, Thibaut / Moullier, Philippe / Le Guiner, Caroline / Adjali, Oumeya

    Human gene therapy

    2019  Band 30, Heft 7, Seite(n) 802–813

    Abstract: Anti-transgene immune responses elicited after intramuscular (i.m.) delivery of recombinant adeno-associated virus (rAAV) have been shown to hamper long-term transgene expression in large-animal models of rAAV-mediated gene transfer. To overcome this ... ...

    Abstract Anti-transgene immune responses elicited after intramuscular (i.m.) delivery of recombinant adeno-associated virus (rAAV) have been shown to hamper long-term transgene expression in large-animal models of rAAV-mediated gene transfer. To overcome this hurdle, an alternative mode of delivery of rAAV vectors in nonhuman primate muscles has been described: the locoregional (LR) intravenous route of administration. Using this injection mode, persistent inducible transgene expression for at least 1 year under the control of the tetracycline-inducible Tet-On system was previously reported in cynomolgus monkeys, with no immunity against the rtTA transgene product. The present study shows the long-term follow-up of these animals. It is reported that LR delivery of a rAAV2/1 vector allows long-term inducible expression up to at least 5 years post gene transfer, with no any detectable host immune response against the transactivator rtTA, despite its immunogenicity following i.m. gene transfer. This study shows for the first time a long-term regulation of muscle gene expression using a Tet-On-inducible system in a large-animal model. Moreover, these findings further confirm that the rAAV LR delivery route is efficient and immunologically safe, allowing long-term skeletal muscle gene transfer.
    Mesh-Begriff(e) Animals ; Antibodies, Viral/immunology ; Cytokines/metabolism ; Dependovirus/genetics ; Dependovirus/immunology ; Follow-Up Studies ; Gene Expression ; Gene Transfer Techniques ; Genetic Vectors/administration & dosage ; Genetic Vectors/adverse effects ; Genetic Vectors/genetics ; Genome, Viral ; Immunity ; Macaca fascicularis ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Time Factors ; Transgenes
    Chemische Substanzen Antibodies, Viral ; Cytokines
    Sprache Englisch
    Erscheinungsdatum 2019-04-16
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1028152-6
    ISSN 1557-7422 ; 1043-0342
    ISSN (online) 1557-7422
    ISSN 1043-0342
    DOI 10.1089/hum.2018.234
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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

    Moreau, Aurélie / Vandamme, Céline / Segovia, Mercedes / Devaux, Marie / Guilbaud, Mickaël / Tilly, Gaëlle / Jaulin, Nicolas / Le Duff, Johanne / Cherel, Yan / Deschamps, Jack-Yves / Anegon, Ignacio / Moullier, Philippe / Cuturi, Maria Cristina / Adjali, Oumeya

    Molecular therapy. Methods & clinical development

    2014  Band 1, Seite(n) 14028

    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)- ... ...

    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 clinical translation. Specific immunomodulation strategies potentially leading to sustained transgene expression while minimizing pharmacological immunosuppression are desirable. Tolerogenic dendritic cells (TolDC) are potential candidates but have not yet been evaluated in the context of gene therapy, to our knowledge. Following intramuscular delivery of rAAV-derived vectors expressing an immunogenic protein in the nonhuman primate model, we assessed the immunomodulating potential of autologous bone marrow-derived TolDC generated in the presence of IL10 and pulsed with the transgene product. TolDC administered either intradermally or intravenously were safe and well tolerated. While the intravenous route showed a modest ability to modulate host immunity against the transgene product, intradermally delivery resulted in a robust vaccination of the macaques when associated to intramuscular rAAV-derived vectors-based gene transfer. These findings demonstrate the critical role of TolDC mode of injection in modulating host immunity. This study also provides the first evidence of the potential of TolDC-based immunomodulation in gene therapy.
    Sprache Englisch
    Erscheinungsdatum 2014-07-23
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2872938-9
    ISSN 2329-0501 ; 2329-0501
    ISSN (online) 2329-0501
    ISSN 2329-0501
    DOI 10.1038/mtm.2014.28
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy.

    Le Guiner, Caroline / Servais, Laurent / Montus, Marie / Larcher, Thibaut / Fraysse, Bodvaël / Moullec, Sophie / Allais, Marine / François, Virginie / Dutilleul, Maeva / Malerba, Alberto / Koo, Taeyoung / Thibaut, Jean-Laurent / Matot, Béatrice / Devaux, Marie / Le Duff, Johanne / Deschamps, Jack-Yves / Barthelemy, Inès / Blot, Stéphane / Testault, Isabelle /
    Wahbi, Karim / Ederhy, Stéphane / Martin, Samia / Veron, Philippe / Georger, Christophe / Athanasopoulos, Takis / Masurier, Carole / Mingozzi, Federico / Carlier, Pierre / Gjata, Bernard / Hogrel, Jean-Yves / Adjali, Oumeya / Mavilio, Fulvio / Voit, Thomas / Moullier, Philippe / Dickson, George

    Nature communications

    2017  Band 8, Seite(n) 16105

    Abstract: Duchenne muscular dystrophy (DMD) is an incurable X-linked muscle-wasting disease caused by mutations in the dystrophin gene. Gene therapy using highly functional microdystrophin genes and recombinant adeno-associated virus (rAAV) vectors is an ... ...

    Abstract Duchenne muscular dystrophy (DMD) is an incurable X-linked muscle-wasting disease caused by mutations in the dystrophin gene. Gene therapy using highly functional microdystrophin genes and recombinant adeno-associated virus (rAAV) vectors is an attractive strategy to treat DMD. Here we show that locoregional and systemic delivery of a rAAV2/8 vector expressing a canine microdystrophin (cMD1) is effective in restoring dystrophin expression and stabilizing clinical symptoms in studies performed on a total of 12 treated golden retriever muscular dystrophy (GRMD) dogs. Locoregional delivery induces high levels of microdystrophin expression in limb musculature and significant amelioration of histological and functional parameters. Systemic intravenous administration without immunosuppression results in significant and sustained levels of microdystrophin in skeletal muscles and reduces dystrophic symptoms for over 2 years. No toxicity or adverse immune consequences of vector administration are observed. These studies indicate safety and efficacy of systemic rAAV-cMD1 delivery in a large animal model of DMD, and pave the way towards clinical trials of rAAV-microdystrophin gene therapy in DMD patients.
    Mesh-Begriff(e) Administration, Intravenous ; Animals ; Dependovirus ; Disease Models, Animal ; Dogs ; Dystrophin/genetics ; Gene Transfer Techniques ; Genetic Therapy ; Genetic Vectors ; Male ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/physiopathology ; Muscular Dystrophy, Animal/genetics ; Muscular Dystrophy, Animal/metabolism ; Muscular Dystrophy, Animal/physiopathology ; Muscular Dystrophy, Animal/therapy ; Muscular Dystrophy, Duchenne/genetics ; Muscular Dystrophy, Duchenne/metabolism ; Muscular Dystrophy, Duchenne/physiopathology ; Transgenes
    Chemische Substanzen Dystrophin
    Sprache Englisch
    Erscheinungsdatum 2017-07-25
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2041-1723
    ISSN (online) 2041-1723
    DOI 10.1038/ncomms16105
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Forelimb treatment in a large cohort of dystrophic dogs supports delivery of a recombinant AAV for exon skipping in Duchenne patients.

    Le Guiner, Caroline / Montus, Marie / Servais, Laurent / Cherel, Yan / Francois, Virginie / Thibaud, Jean-Laurent / Wary, Claire / Matot, Béatrice / Larcher, Thibaut / Guigand, Lydie / Dutilleul, Maeva / Domenger, Claire / Allais, Marine / Beuvin, Maud / Moraux, Amélie / Le Duff, Johanne / Devaux, Marie / Jaulin, Nicolas / Guilbaud, Mickaël /
    Latournerie, Virginie / Veron, Philippe / Boutin, Sylvie / Leborgne, Christian / Desgue, Diana / Deschamps, Jack-Yves / Moullec, Sophie / Fromes, Yves / Vulin, Adeline / Smith, Richard H / Laroudie, Nicolas / Barnay-Toutain, Frédéric / Rivière, Christel / Bucher, Stéphanie / Le, Thanh-Hoa / Delaunay, Nicolas / Gasmi, Mehdi / Kotin, Robert M / Bonne, Gisèle / Adjali, Oumeya / Masurier, Carole / Hogrel, Jean-Yves / Carlier, Pierre / Moullier, Philippe / Voit, Thomas

    Molecular therapy : the journal of the American Society of Gene Therapy

    2014  Band 22, Heft 11, Seite(n) 1923–1935

    Abstract: Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder caused by mutations in the dystrophin gene, without curative treatment yet available. Our study provides, for the first time, the overall safety profile and therapeutic dose of a ... ...

    Abstract Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder caused by mutations in the dystrophin gene, without curative treatment yet available. Our study provides, for the first time, the overall safety profile and therapeutic dose of a recombinant adeno-associated virus vector, serotype 8 (rAAV8) carrying a modified U7snRNA sequence promoting exon skipping to restore a functional in-frame dystrophin transcript, and injected by locoregional transvenous perfusion of the forelimb. Eighteen Golden Retriever Muscular Dystrophy (GRMD) dogs were exposed to increasing doses of GMP-manufactured vector. Treatment was well tolerated in all, and no acute nor delayed adverse effect, including systemic and immune toxicity was detected. There was a dose relationship for the amount of exon skipping with up to 80% of myofibers expressing dystrophin at the highest dose. Similarly, histological, nuclear magnetic resonance pathological indices and strength improvement responded in a dose-dependent manner. The systematic comparison of effects using different independent methods, allowed to define a minimum threshold of dystrophin expressing fibers (>33% for structural measures and >40% for strength) under which there was no clear-cut therapeutic effect. Altogether, these results support the concept of a phase 1/2 trial of locoregional delivery into upper limbs of nonambulatory DMD patients.
    Mesh-Begriff(e) Animals ; Cohort Studies ; Dependovirus/genetics ; Disease Models, Animal ; Dogs ; Dose-Response Relationship, Drug ; Dystrophin/genetics ; Exons ; Forelimb/physiopathology ; Genetic Therapy ; Genetic Vectors/administration & dosage ; Humans ; Infusions, Intravenous ; Muscular Dystrophy, Duchenne/genetics ; Muscular Dystrophy, Duchenne/physiopathology ; Muscular Dystrophy, Duchenne/therapy ; RNA, Small Nuclear/genetics ; RNA, Small Nuclear/metabolism
    Chemische Substanzen Dystrophin ; RNA, Small Nuclear ; U7 small nuclear RNA
    Sprache Englisch
    Erscheinungsdatum 2014-08-04
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1038/mt.2014.151
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5640: Hefte anzeigen Standort:
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  8. Artikel: Generation and in vivo evaluation of IL10-treated dendritic cells in a nonhuman primate model of AAV-based gene transfer.

    Moreau, / Vandamme, C / Segovia, Mercedes / DEVAUX, / Guilbaud, Mickaël / Tilly, Gaëlle / Jaulin, Nicolas / Le Duff, Johanne / Cherel, Yan / Deschamps, Jack-Yves / Anegon, Ignacio / Moullier, Philippe / Cuturi, Maria Cristina / Adjali, Oumeya

    Mol Ther Methods Clin Dev (1), . (2014)

    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)- ... ...

    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 clinical translation. Specific immunomodulation strategies potentially leading to sustained transgene expression while minimizing pharmacological immunosuppression are desirable. Tolerogenic dendritic cells (TolDC) are potential candidates but have not yet been evaluated in the context of gene therapy, to our knowledge. Following intramuscular delivery of rAAV-derived vectors expressing an immunogenic protein in the nonhuman primate model, we assessed the immunomodulating potential of autologous bone marrow-derived TolDC generated in the presence of IL10 and pulsed with the transgene product. TolDC administered either intradermally or intravenously were safe and well tolerated. While the intravenous route showed a modest ability to modulate host immunity against the transgene product, intradermally delivery resulted in a robust vaccination of the macaques when associated to intramuscular rAAV-derived vectors-based gene transfer. These findings demonstrate the critical role of TolDC mode of injection in modulating host immunity. This study also provides the first evidence of the potential of TolDC-based immunomodulation in gene therapy.
    Sprache Englisch
    Dokumenttyp Artikel
    Datenquelle AGRIS - International Information System for the Agricultural Sciences and Technology

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

    Moreau, / Vandamme, C / Segovia, Mercedes / DEVAUX, / Guilbaud, Mickaël / Tilly, Gaëlle / Jaulin, Nicolas / Le Duff, Johanne / Cherel, Yan / Deschamps, Jack-Yves / Anegon, Ignacio / Moullier, Philippe / Cuturi, Maria Cristina / Adjali, Oumeya

    Mol Ther Methods Clin Dev (1), . (2014)

    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)- ... ...

    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 clinical translation. Specific immunomodulation strategies potentially leading to sustained transgene expression while minimizing pharmacological immunosuppression are desirable. Tolerogenic dendritic cells (TolDC) are potential candidates but have not yet been evaluated in the context of gene therapy, to our knowledge. Following intramuscular delivery of rAAV-derived vectors expressing an immunogenic protein in the nonhuman primate model, we assessed the immunomodulating potential of autologous bone marrow-derived TolDC generated in the presence of IL10 and pulsed with the transgene product. TolDC administered either intradermally or intravenously were safe and well tolerated. While the intravenous route showed a modest ability to modulate host immunity against the transgene product, intradermally delivery resulted in a robust vaccination of the macaques when associated to intramuscular rAAV-derived vectors-based gene transfer. These findings demonstrate the critical role of TolDC mode of injection in modulating host immunity. This study also provides the first evidence of the potential of TolDC-based immunomodulation in gene therapy.
    Sprache Englisch
    Dokumenttyp Artikel
    Datenquelle AGRIS - International Information System for the Agricultural Sciences and Technology

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