Fusion of HIV-1 Tat protein transduction domain to poly-lysine as a new DNA delivery tool.
Identifieur interne : 001F14 ( Main/Exploration ); précédent : 001F13; suivant : 001F15Fusion of HIV-1 Tat protein transduction domain to poly-lysine as a new DNA delivery tool.
Auteurs : H. Hashida [Japon] ; M. Miyamoto ; Y. Cho ; Y. Hida ; K. Kato ; T. Kurokawa ; S. Okushiba ; S. Kondo ; H. Dosaka-Akita ; H. KatohSource :
- British journal of cancer [ 0007-0920 ] ; 2004.
Descripteurs français
- KwdFr :
- Carcinome épidermoïde (anatomopathologie), Carcinomes (anatomopathologie), Cellules cancéreuses en culture, Fragments peptidiques, Gènes rapporteurs, Humains, Lignée cellulaire, Polylysine (génétique), Produits du gène tat du virus de l'immunodéficience humaine, Protéines de fusion recombinantes, Protéines du gène tat, Techniques de transfert de gènes, Thérapie génétique (), Tumeurs de l'oesophage (anatomopathologie), Tumeurs du pancréas (anatomopathologie), Tumeurs du poumon (anatomopathologie).
- MESH :
- anatomopathologie : Carcinome épidermoïde, Carcinomes, Tumeurs de l'oesophage, Tumeurs du pancréas, Tumeurs du poumon.
- génétique : Polylysine.
- Cellules cancéreuses en culture, Fragments peptidiques, Gènes rapporteurs, Humains, Lignée cellulaire, Produits du gène tat du virus de l'immunodéficience humaine, Protéines de fusion recombinantes, Protéines du gène tat, Techniques de transfert de gènes, Thérapie génétique.
English descriptors
- KwdEn :
- Carcinoma (pathology), Carcinoma, Squamous Cell (pathology), Cell Line, Esophageal Neoplasms (pathology), Gene Products, tat, Gene Transfer Techniques, Genes, Reporter, Genetic Therapy (methods), Humans, Lung Neoplasms (pathology), Pancreatic Neoplasms (pathology), Peptide Fragments, Polylysine (genetics), Recombinant Fusion Proteins, Tumor Cells, Cultured, tat Gene Products, Human Immunodeficiency Virus.
- MESH :
- chemical , genetics : Polylysine.
- chemical : Gene Products, tat, Peptide Fragments, Recombinant Fusion Proteins, tat Gene Products, Human Immunodeficiency Virus.
- methods : Genetic Therapy.
- pathology : Carcinoma, Carcinoma, Squamous Cell, Esophageal Neoplasms, Lung Neoplasms, Pancreatic Neoplasms.
- Cell Line, Gene Transfer Techniques, Genes, Reporter, Humans, Tumor Cells, Cultured.
Abstract
Effective gene therapy depends on the efficient transfer of therapeutic genes to target cells. None of the current technologies, however, satisfy all of the requirements necessary for gene therapy, because the plasma and nuclear membranes of mammalian cells are tight barriers against gene transfer using synthetic delivery systems. The protein transduction domain (PTD) of human immunodeficiency virus type 1 (HIV-1) Tat protein greatly facilitates protein transfer via membrane destabilisation. We synthesised polylysine peptides containing Tat PTD (TAT-pK), or other sequences, and investigated their potential as agents for gene transfer. The synthesised polypeptide TAT-pK retains DNA binding function and mediates delivery of a reporter gene to cultured cells. RGD motif binds with low affinity to alpha integrins which induce cell activation. Two control polypeptides, GGG-pK and RGD-pK, were synthesised and tested, but their gene transfer abilities were weaker than those of TAT-pK. TAT-pK-mediated gene transfer was enhanced in the presence of chloroquine or ammonium chloride, to a greater extent than that of cationic lipid-mediated gene transfer in most cancer cell lines tested. These data suggest that TAT-pK may be a potent candidate delivery vehicle that promotes gene transfer, dependent on the endocytic pathway. We conclude that the TAT-pK/DNA complex is useful as a minimal unit to package therapeutic genes and to transduce them into mammalian cells.
DOI: 10.1038/sj.bjc.6601680
PubMed: 15026809
Affiliations:
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Le document en format XML
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<series><title level="j">British journal of cancer</title>
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<term>Carcinoma, Squamous Cell (pathology)</term>
<term>Cell Line</term>
<term>Esophageal Neoplasms (pathology)</term>
<term>Gene Products, tat</term>
<term>Gene Transfer Techniques</term>
<term>Genes, Reporter</term>
<term>Genetic Therapy (methods)</term>
<term>Humans</term>
<term>Lung Neoplasms (pathology)</term>
<term>Pancreatic Neoplasms (pathology)</term>
<term>Peptide Fragments</term>
<term>Polylysine (genetics)</term>
<term>Recombinant Fusion Proteins</term>
<term>Tumor Cells, Cultured</term>
<term>tat Gene Products, Human Immunodeficiency Virus</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Carcinome épidermoïde (anatomopathologie)</term>
<term>Carcinomes (anatomopathologie)</term>
<term>Cellules cancéreuses en culture</term>
<term>Fragments peptidiques</term>
<term>Gènes rapporteurs</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Polylysine (génétique)</term>
<term>Produits du gène tat du virus de l'immunodéficience humaine</term>
<term>Protéines de fusion recombinantes</term>
<term>Protéines du gène tat</term>
<term>Techniques de transfert de gènes</term>
<term>Thérapie génétique ()</term>
<term>Tumeurs de l'oesophage (anatomopathologie)</term>
<term>Tumeurs du pancréas (anatomopathologie)</term>
<term>Tumeurs du poumon (anatomopathologie)</term>
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<term>Peptide Fragments</term>
<term>Recombinant Fusion Proteins</term>
<term>tat Gene Products, Human Immunodeficiency Virus</term>
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<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Carcinome épidermoïde</term>
<term>Carcinomes</term>
<term>Tumeurs de l'oesophage</term>
<term>Tumeurs du pancréas</term>
<term>Tumeurs du poumon</term>
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<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Genetic Therapy</term>
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<term>Carcinoma, Squamous Cell</term>
<term>Esophageal Neoplasms</term>
<term>Lung Neoplasms</term>
<term>Pancreatic Neoplasms</term>
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<term>Gene Transfer Techniques</term>
<term>Genes, Reporter</term>
<term>Humans</term>
<term>Tumor Cells, Cultured</term>
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<keywords scheme="MESH" xml:lang="fr"><term>Cellules cancéreuses en culture</term>
<term>Fragments peptidiques</term>
<term>Gènes rapporteurs</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Produits du gène tat du virus de l'immunodéficience humaine</term>
<term>Protéines de fusion recombinantes</term>
<term>Protéines du gène tat</term>
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<front><div type="abstract" xml:lang="en">Effective gene therapy depends on the efficient transfer of therapeutic genes to target cells. None of the current technologies, however, satisfy all of the requirements necessary for gene therapy, because the plasma and nuclear membranes of mammalian cells are tight barriers against gene transfer using synthetic delivery systems. The protein transduction domain (PTD) of human immunodeficiency virus type 1 (HIV-1) Tat protein greatly facilitates protein transfer via membrane destabilisation. We synthesised polylysine peptides containing Tat PTD (TAT-pK), or other sequences, and investigated their potential as agents for gene transfer. The synthesised polypeptide TAT-pK retains DNA binding function and mediates delivery of a reporter gene to cultured cells. RGD motif binds with low affinity to alpha integrins which induce cell activation. Two control polypeptides, GGG-pK and RGD-pK, were synthesised and tested, but their gene transfer abilities were weaker than those of TAT-pK. TAT-pK-mediated gene transfer was enhanced in the presence of chloroquine or ammonium chloride, to a greater extent than that of cationic lipid-mediated gene transfer in most cancer cell lines tested. These data suggest that TAT-pK may be a potent candidate delivery vehicle that promotes gene transfer, dependent on the endocytic pathway. We conclude that the TAT-pK/DNA complex is useful as a minimal unit to package therapeutic genes and to transduce them into mammalian cells.</div>
</front>
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<name sortKey="Hida, Y" sort="Hida, Y" uniqKey="Hida Y" first="Y" last="Hida">Y. Hida</name>
<name sortKey="Kato, K" sort="Kato, K" uniqKey="Kato K" first="K" last="Kato">K. Kato</name>
<name sortKey="Katoh, H" sort="Katoh, H" uniqKey="Katoh H" first="H" last="Katoh">H. Katoh</name>
<name sortKey="Kondo, S" sort="Kondo, S" uniqKey="Kondo S" first="S" last="Kondo">S. Kondo</name>
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<name sortKey="Okushiba, S" sort="Okushiba, S" uniqKey="Okushiba S" first="S" last="Okushiba">S. Okushiba</name>
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<country name="Japon"><noRegion><name sortKey="Hashida, H" sort="Hashida, H" uniqKey="Hashida H" first="H" last="Hashida">H. Hashida</name>
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