Abstract
Delivery of therapeutic proteins into tissues and across the blood-brain barrier is severely limited by the size and biochemical properties of the proteins. Here it is shown that intraperitoneal injection of the 120-kilodalton beta-galactosidase protein, fused to the protein transduction domain from the human immunodeficiency virus TAT protein, results in delivery of the biologically active fusion protein to all tissues in mice, including the brain. These results open new possibilities for direct delivery of proteins into patients in the context of protein therapy, as well as for epigenetic experimentation with model organisms.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Blood-Brain Barrier
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Brain / metabolism
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Cell Membrane / metabolism
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Drug Carriers
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Drug Delivery Systems*
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Fluorescein-5-isothiocyanate
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Gene Products, tat / administration & dosage
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Gene Products, tat / metabolism*
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Humans
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Injections, Intraperitoneal
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Jurkat Cells
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Lipid Bilayers
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Mice
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Mice, Inbred C57BL
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Microscopy, Confocal
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Microscopy, Fluorescence
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Muscle, Skeletal / metabolism
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / metabolism*
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Spleen / metabolism
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Tissue Distribution
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Tumor Cells, Cultured
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beta-Galactosidase / administration & dosage
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beta-Galactosidase / metabolism*
Substances
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Drug Carriers
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Gene Products, tat
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Lipid Bilayers
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Recombinant Fusion Proteins
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beta-Galactosidase
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Fluorescein-5-isothiocyanate