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  1. Book ; Online ; Thesis: Entwicklung von delivery-Systemen für oligomere Nukleinsäurewirkstoffe

    Veldhoen, Sandra

    2005  

    Author's details vorgelegt von Sandra Veldhoen
    Language German
    Size Online-Ressource
    Document type Book ; Online ; Thesis
    Thesis / German Habilitation thesis Univ., Diss--Lübeck, 2006
    Database Former special subject collection: coastal and deep sea fishing

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  2. Book ; Online ; Thesis: Entwicklung von delivery-Systemen für oligomere Nukleinsäurewirkstoffe

    Veldhoen, Sandra [Verfasser]

    2005  

    Author's details vorgelegt von Sandra Veldhoen
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  3. Article ; Online: Recent developments in peptide-based nucleic acid delivery.

    Veldhoen, Sandra / Laufer, Sandra D / Restle, Tobias

    International journal of molecular sciences

    2008  Volume 9, Issue 7, Page(s) 1276–1320

    Abstract: Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among ...

    Abstract Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cell-penetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10-30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisense-oligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls.
    Keywords covid19
    Language English
    Publishing date 2008-07-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms9071276
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Recent Developments in Peptide-Based Nucleic Acid Delivery

    Tobias Restle / Sandra D. Laufer / Sandra Veldhoen

    International Journal of Molecular Sciences, Vol 9, Iss 7, Pp 1276-

    2008  Volume 1320

    Abstract: Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among ...

    Abstract Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cellpenetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10-30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisenseoligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls.
    Keywords cell-penetrating peptides ; nucleic acid drugs ; nucleic acid delivery ; endocytosis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 612
    Language English
    Publishing date 2008-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Cellular delivery of small interfering RNA by a non-covalently attached cell-penetrating peptide: quantitative analysis of uptake and biological effect.

    Veldhoen, Sandra / Laufer, Sandra D / Trampe, Alexander / Restle, Tobias

    Nucleic acids research

    2006  Volume 34, Issue 22, Page(s) 6561–6573

    Abstract: Cell-penetrating peptides (CPPs) have evolved as promising new tools to deliver nucleic acids into cells. So far, the majority of these delivery systems require a covalent linkage between carrier and cargo. To exploit the higher flexibility of a non- ... ...

    Abstract Cell-penetrating peptides (CPPs) have evolved as promising new tools to deliver nucleic acids into cells. So far, the majority of these delivery systems require a covalent linkage between carrier and cargo. To exploit the higher flexibility of a non-covalent strategy, we focused on the characterisation of a novel carrier peptide termed MPGalpha, which spontaneously forms complexes with nucleic acids. Using a luciferase-targeted small interfering RNA (siRNA) as cargo, we optimised the conditions for MPGalpha-mediated transfection of mammalian cells. In this system, reporter gene activity could be inhibited up to 90% with an IC50 value in the sub-nanomolar range. As a key issue, we addressed the cellular uptake mechanism of MPGalpha/siRNA complexes applying various approaches. First, transfection of HeLa cells with MPGalpha/siRNA complexes in the presence of several inhibitors of endocytosis showed a significant reduction of the RNA interference (RNAi) effect. Second, confocal laser microscopy revealed a punctual intracellular pattern rather than a diffuse distribution of fluorescently labelled RNA-cargo. These data provide strong evidence of an endocytotic pathway contributing significantly to the uptake of MPGalpha/siRNA complexes. Finally, we quantified the intracellular number of siRNA molecules after MPGalpha-mediated transfection. The amount of siRNA required to induce half maximal RNAi was 10 000 molecules per cell. Together, the combination of methods provided allows for a detailed side by side quantitative analysis of cargo internalisation and related biological effects. Thus, the overall efficiency of a given delivery technique as well as the mechanism of uptake can be assessed.
    MeSH term(s) Biological Transport ; Cell Line ; Cell Membrane/metabolism ; Endocytosis ; Genes, Reporter ; HeLa Cells ; Humans ; Peptides/chemistry ; RNA Interference ; RNA, Small Interfering/metabolism ; Transfection
    Chemical Substances MPGalpha peptide ; Peptides ; RNA, Small Interfering
    Language English
    Publishing date 2006-11-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkl941
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1067: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Noncovalent peptide-mediated delivery of chemically modified steric block oligonucleotides promotes splice correction: quantitative analysis of uptake and biological effect.

    Laufer, Sandra D / Recke, Anna Lena / Veldhoen, Sandra / Trampe, Alexander / Restle, Tobias

    Oligonucleotides

    2009  Volume 19, Issue 1, Page(s) 63–80

    Abstract: Despite numerous encouraging reports in the literature, the efficiency of cell penetrating peptides (CPPs) in promoting cellular delivery of bioactive cargos is still limited. To extend our current understanding of the underlying limitations of such ... ...

    Abstract Despite numerous encouraging reports in the literature, the efficiency of cell penetrating peptides (CPPs) in promoting cellular delivery of bioactive cargos is still limited. To extend our current understanding of the underlying limitations of such approaches, we performed quantitative uptake studies of different chemically modified (2'-O-methyl, LNA and PNA) steric block oligonucleotides, targeted against a mutated splice site inserted in a firefly luciferase reporter gene construct, applying the peptide carrier MPGalpha as a model system. The peptide formed stable noncovalent complexes with phosphorothioate oligonucleotide (PTO) and locked nucleic acid (LNA) modified oligonucleotides, whereas the neutral peptide nucleic acid (PNA) had to be hybridized to an unmodified DNA to allow for complex formation. Detailed quantitative uptake studies revealed comparable numbers of intracellular PTO and LNA oligonucleotides after peptide-mediated delivery. Surprisingly, the PTO derivative showed the strongest upregulation of reporter gene activity of about 100-fold followed by the PNA (40-fold) and LNA (10-fold). Electroporation and microinjection studies proved that delivery itself was not the limiting factor for the low activity of the LNA derivative. Maximal achievable reporter gene activity could be observed only after addition of chloroquine (CQ), indicative of an endosomal pathway involved. This is in line with nuclear microinjection experiments, which show that the minimal number of steric block molecules needed to trigger the observed reporter upregulation is about two orders of magnitude lower than determined after peptide or cationic lipid delivery.
    MeSH term(s) Amino Acid Sequence ; Electrophoretic Mobility Shift Assay ; Electroporation ; HeLa Cells ; Humans ; Microscopy, Fluorescence ; Molecular Sequence Data ; Oligonucleotides/administration & dosage ; Peptides/analysis ; Peptides/chemistry ; Reverse Transcriptase Polymerase Chain Reaction
    Chemical Substances Oligonucleotides ; Peptides
    Language English
    Publishing date 2009-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126165-9
    ISSN 1557-8526 ; 1545-4576
    ISSN (online) 1557-8526
    ISSN 1545-4576
    DOI 10.1089/oli.2008.0160
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3253: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: 3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine.

    Clement, Cristina C / D'Alessandro, Angelo / Thangaswamy, Sangeetha / Chalmers, Samantha / Furtado, Raquel / Spada, Sheila / Mondanelli, Giada / Ianni, Federica / Gehrke, Sarah / Gargaro, Marco / Manni, Giorgia / Cara, Luisa Carlota Lopez / Runge, Peter / Tsai, Wanxia Li / Karaman, Sinem / Arasa, Jorge / Fernandez-Rodriguez, Ruben / Beck, Amanda / Macchiarulo, Antonio /
    Gadina, Massimo / Halin, Cornelia / Fallarino, Francesca / Skobe, Mihaela / Veldhoen, Marc / Moretti, Simone / Formenti, Silvia / Demaria, Sandra / Soni, Rajesh K / Galarini, Roberta / Sardella, Roccaldo / Lauvau, Gregoire / Putterman, Chaim / Alitalo, Kari / Grohmann, Ursula / Santambrogio, Laura

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 4447

    Abstract: Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-L-kynurenamine (3-HKA) is a biogenic amine produced via ... ...

    Abstract Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-L-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1/NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1β, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8
    MeSH term(s) Animals ; Biogenic Amines/metabolism ; Biogenic Amines/pharmacology ; Biogenic Amines/therapeutic use ; Cell Line, Tumor ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Disease Models, Animal ; Endothelial Cells ; Humans ; Immunomodulation/drug effects ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics ; Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology ; Inflammation ; Interferon-gamma/pharmacology ; Kynurenine/analogs & derivatives ; Kynurenine/metabolism ; Kynurenine/pharmacology ; Kynurenine/therapeutic use ; Mice ; NF-kappa B/metabolism ; Nephritis/drug therapy ; Nephritis/immunology ; Psoriasis/drug therapy ; Psoriasis/immunology ; Tryptophan/metabolism
    Chemical Substances Biogenic Amines ; IDO1 protein, mouse ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; NF-kappa B ; 3-hydroxykynurenine (27723548JL) ; Kynurenine (343-65-7) ; Interferon-gamma (82115-62-6) ; Tryptophan (8DUH1N11BX)
    Language English
    Publishing date 2021-07-21
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-24785-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Cellular delivery of small interfering RNA by a non-covalently attached cell-penetrating peptide: quantitative analysis of uptake and biological effect

    Veldhoen, Sandra / Laufer, Sandra D / Trampe, Alexander / Restle, Tobias

    Nucleic acids research. 2006 Dec., v. 34, no. 22

    2006  

    Abstract: Cell-penetrating peptides (CPPs) have evolved as promising new tools to deliver nucleic acids into cells. So far, the majority of these delivery systems require a covalent linkage between carrier and cargo. To exploit the higher flexibility of a non- ... ...

    Abstract Cell-penetrating peptides (CPPs) have evolved as promising new tools to deliver nucleic acids into cells. So far, the majority of these delivery systems require a covalent linkage between carrier and cargo. To exploit the higher flexibility of a non-covalent strategy, we focused on the characterisation of a novel carrier peptide termed MPGα, which spontaneously forms complexes with nucleic acids. Using a luciferase-targeted small interfering RNA (siRNA) as cargo, we optimised the conditions for MPGα-mediated transfection of mammalian cells. In this system, reporter gene activity could be inhibited up to 90% with an IC₅₀ value in the sub-nanomolar range. As a key issue, we addressed the cellular uptake mechanism of MPGα/siRNA complexes applying various approaches. First, transfection of HeLa cells with MPGα/siRNA complexes in the presence of several inhibitors of endocytosis showed a significant reduction of the RNA interference (RNAi) effect. Second, confocal laser microscopy revealed a punctual intracellular pattern rather than a diffuse distribution of fluorescently labelled RNA-cargo. These data provide strong evidence of an endocytotic pathway contributing significantly to the uptake of MPGα/siRNA complexes. Finally, we quantified the intracellular number of siRNA molecules after MPGα-mediated transfection. The amount of siRNA required to induce half maximal RNAi was 10 000 molecules per cell. Together, the combination of methods provided allows for a detailed side by side quantitative analysis of cargo internalisation and related biological effects. Thus, the overall efficiency of a given delivery technique as well as the mechanism of uptake can be assessed.
    Keywords RNA interference ; bioactive properties ; chemical elements ; confocal laser scanning microscopy ; endocytosis ; inhibitory concentration 50 ; mammals ; peptides ; quantitative analysis ; reporter genes ; small interfering RNA ; transfection
    Language English
    Dates of publication 2006-12
    Size p. 6561-6573.
    Document type Article
    ZDB-ID 186809-3
    ISSN 0301-5610 ; 0305-1048
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkl941
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 79/704: Show issues

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  9. Article ; Online: 3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine

    Cristina C. Clement / Angelo D’Alessandro / Sangeetha Thangaswamy / Samantha Chalmers / Raquel Furtado / Sheila Spada / Giada Mondanelli / Federica Ianni / Sarah Gehrke / Marco Gargaro / Giorgia Manni / Luisa Carlota Lopez Cara / Peter Runge / Wanxia Li Tsai / Sinem Karaman / Jorge Arasa / Ruben Fernandez-Rodriguez / Amanda Beck / Antonio Macchiarulo /
    Massimo Gadina / Cornelia Halin / Francesca Fallarino / Mihaela Skobe / Marc Veldhoen / Simone Moretti / Silvia Formenti / Sandra Demaria / Rajesh K. Soni / Roberta Galarini / Roccaldo Sardella / Gregoire Lauvau / Chaim Putterman / Kari Alitalo / Ursula Grohmann / Laura Santambrogio

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 17

    Abstract: 3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. Here the authors identify 3-HKA as a biogenic amine and show it has anti-inflammatory properties that can protect mice against psoriasis and ... ...

    Abstract 3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. Here the authors identify 3-HKA as a biogenic amine and show it has anti-inflammatory properties that can protect mice against psoriasis and nephrotoxic nephritis.
    Keywords Science ; Q
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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