Targeted retroviral vectors displaying a cleavage site-engineered hemagglutinin (HA) through HA-protease interactions
| Autor: | Christian J. Buchholz, Els Verhoeyen, Judit Szécsi, Rosybel Drury, Richard Schneider, Jean-Luc Coll, Stephen J. Russell, Irene Hartl, Bertrand Boson, Véronique Josserand, François-Loïc Cosset, Marie Pierre Grange |
|---|---|
| Přispěvatelé: | Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de Recherche Sur Le Cancer du Poumon : Bases Moléculaires de la Progression Tumorale, Dépistage et Thérapie Génique, Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale (INSERM), Medizinische Biotechnologie, Paul-Ehrlich Institut, Mayo Clinic, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Salas, Danielle |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
MESH: Matrix Metalloproteinases
MESH: Factor Xa medicine.medical_treatment Genetic enhancement Cell Hemagglutinin Glycoproteins Influenza Virus MESH: Amino Acid Sequence Protein Engineering Substrate Specificity 0302 clinical medicine MESH: Genetic Vectors Neoplasms Drug Discovery Chlorocebus aethiops MESH: Animals MESH: Neoplasms 0303 health sciences MESH: Hemagglutinin Glycoproteins Influenza Virus Metalloendopeptidases MESH: Leukemia Virus Murine Leukemia Virus Murine MESH: Protein Engineering medicine.anatomical_structure 030220 oncology & carcinogenesis Factor Xa Molecular Medicine Protein Binding Proteases MESH: Enzyme Activation Genetic Vectors Molecular Sequence Data MESH: Metalloendopeptidases [SDV.CAN]Life Sciences [q-bio]/Cancer Gene delivery Biology Cleavage (embryo) Cell Line 03 medical and health sciences [SDV.CAN] Life Sciences [q-bio]/Cancer Genetics medicine Animals Humans MESH: Protein Binding Amino Acid Sequence Molecular Biology 030304 developmental biology Pharmacology Protease MESH: Molecular Sequence Data MESH: Humans Molecular biology MESH: Cercopithecus aethiops In vitro Matrix Metalloproteinases MESH: Cell Line Enzyme Activation Cell culture MESH: Substrate Specificity |
| Zdroj: | Molecular Therapy Molecular Therapy, Cell Press, 2006, 14 (5), pp.735-44. ⟨10.1016/j.ymthe.2006.04.007⟩ Molecular Therapy, 2006, 14 (5), pp.735-44. ⟨10.1016/j.ymthe.2006.04.007⟩ |
| ISSN: | 1525-0016 1525-0024 |
| DOI: | 10.1016/j.ymthe.2006.04.007⟩ |
| Popis: | International audience; We report here a targeting method that exploits the expression pattern of cell surface proteases to induce gene delivery to specific tissues. We describe retroviral vectors harboring modified surface glycoproteins derived from an avian influenza virus hemagglutinin (HA) for which the cell entry properties, dependent on HA cleavage by producer cells, were conditionally blocked at a postbinding step by insertion of matrix metalloproteinase (MMP) substrates. We demonstrate that such vectors induce gene transfer, both in vitro and in mice harboring human tumor xenografts, only through contact with target cells expressing MMPs that cleave the substrate introduced into the recombinant HA. This selective gene transfer in MMP-rich cells was specifically inhibited by 1,10-phenanthroline, a broad-range MMP inhibitor. Importantly, such MMP-activatable vectors selectively transduced MMP-rich cells in heterogeneous populations containing MMP-rich and MMP-poor cells. These vectors will allow useful gene transfer applications into target cells exhibiting specific protease activities. |
| Databáze: | OpenAIRE |
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