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Science 3 September 1999:
Vol. 285. no. 5433, pp. 1569 - 1572
DOI: 10.1126/science.285.5433.1569
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Reports

In Vivo Protein Transduction: Delivery of a Biologically Active Protein into the Mouse

Steven R. Schwarze, Alan Ho, Adamina Vocero-Akbani, Steven F. Dowdy *

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.

Howard Hughes Medical Institute and Departments of Pathology and Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
*   To whom correspondence should be addressed. E-mail: dowdy{at}pathology.wustl.edu

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E. L. Snyder, C. C. Saenz, C. Denicourt, B. R. Meade, X.-S. Cui, I. M. Kaplan, and S. F. Dowdy (2005)
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   Abstract »    Full Text »    PDF »
p21-activated kinase (Pak) regulates NADPH oxidase activation in human neutrophils.
K. D. Martyn, M.-J. Kim, M. T. Quinn, M. C. Dinauer, and U. G. Knaus (2005)
Blood 106, 3962-3969
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Nucleus Accumbens Long-Term Depression and the Expression of Behavioral Sensitization.
K. Brebner, T. P. Wong, L. Liu, Y. Liu, P. Campsall, S. Gray, L. Phelps, A. G. Phillips, and Y. T. Wang (2005)
Science 310, 1340-1343
   Abstract »    Full Text »    PDF »
BETA2/NeuroD Protein Can Be Transduced Into Cells Due to an Arginine- and Lysine-Rich Sequence.
H. Noguchi, S. Bonner-Weir, F.-Y. Wei, M. Matsushita, and S. Matsumoto (2005)
Diabetes 54, 2859-2866
   Abstract »    Full Text »    PDF »
Characterization of a possible amyloidogenic precursor in glutamine-repeat neurodegenerative diseases.
R. S. Armen, B. M. Bernard, R. Day, D. O. V. Alonso, and V. Daggett (2005)
PNAS 102, 13433-13438
   Abstract »    Full Text »    PDF »
Penetratin Improves Tumor Retention of Single-Chain Antibodies: A Novel Step toward Optimization of Radioimmunotherapy of Solid Tumors.
M. Jain, S. C. Chauhan, A. P. Singh, G. Venkatraman, D. Colcher, and S. K. Batra (2005)
Cancer Res. 65, 7840-7846
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Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides.
S. Tripathi, B. Chaubey, S. Ganguly, D. Harris, R. A Casale, and V. N. Pandey (2005)
Nucleic Acids Res. 33, 4345-4356
   Abstract »    Full Text »    PDF »
Characterization of the role of CaMKI-like kinase (CKLiK) in human granulocyte function.
S. Verploegen, L. Ulfman, H. W. M. van Deutekom, C. van Aalst, H. Honing, J.-W. J. Lammers, L. Koenderman, and P. J. Coffer (2005)
Blood 106, 1076-1083
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A novel Rho-mDia2-HDAC6 pathway controls podosome patterning through microtubule acetylation in osteoclasts.
O. Destaing, F. Saltel, B. Gilquin, A. Chabadel, S. Khochbin, S. Ory, and P. Jurdic (2005)
J. Cell Sci. 118, 2901-2911
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A Novel Inhibitor of N-Ethylmaleimide-Sensitive Factor Decreases Leukocyte Trafficking and Peritonitis.
C. N. Morrell, K. Matsushita, and C. J. Lowenstein (2005)
J. Pharmacol. Exp. Ther. 314, 155-161
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Coronin-1 Function Is Required for Phagosome Formation.
M. Yan, R. F. Collins, S. Grinstein, and W. S. Trimble (2005)
Mol. Biol. Cell 16, 3077-3087
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Inhibition of Stat3 activation in the endometrium prevents implantation: A nonsteroidal approach to contraception.
R. D. Catalano, M. H. Johnson, E. A. Campbell, D. S. Charnock-Jones, S. K. Smith, and A. M. Sharkey (2005)
PNAS 102, 8585-8590
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Protein Transduction Assisted by Polyethylenimine-Cationized Carrier Proteins.
M. Kitazoe, H. Murata, J. Futami, T. Maeda, M. Sakaguchi, M. Miyazaki, M. Kosaka, H. Tada, M. Seno, N.-h. Huh, et al. (2005)
J. Biochem. 137, 693-701
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Delivery of {beta}-Galactosidase to Mouse Brain via the Blood-Brain Barrier Transferrin Receptor.
Y. Zhang and W. M. Pardridge (2005)
J. Pharmacol. Exp. Ther. 313, 1075-1081
   Abstract »    Full Text »    PDF »
Transduction of phosphorylated heat shock-related protein 20, HSP20, prevents vasospasm of human umbilical artery smooth muscle.
C. R. Flynn, C. M. Brophy, E. J. Furnish, P. Komalavilas, D. Tessier, J. Thresher, and L. Joshi (2005)
J Appl Physiol 98, 1836-1845
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Cellular Uptake of Unconjugated TAT Peptide Involves Clathrin-dependent Endocytosis and Heparan Sulfate Receptors.
J. P. Richard, K. Melikov, H. Brooks, P. Prevot, B. Lebleu, and L. V. Chernomordik (2005)
J. Biol. Chem. 280, 15300-15306
   Abstract »    Full Text »    PDF »
Transduction of the Scorpion Toxin Maurocalcine into Cells: EVIDENCE THAT THE TOXIN CROSSES THE PLASMA MEMBRANE.
E. Esteve, K. Mabrouk, A. Dupuis, S. Smida-Rezgui, X. Altafaj, D. Grunwald, J.-C. Platel, N. Andreotti, I. Marty, J.-M. Sabatier, et al. (2005)
J. Biol. Chem. 280, 12833-12839
   Abstract »    Full Text »    PDF »
A Novel Class of Fusion Polypeptides Inhibits Exocytosis.
K. Matsushita, C. N. Morrell, and C. J. Lowenstein (2005)
Mol. Pharmacol. 67, 1137-1144
   Abstract »    Full Text »    PDF »
The Scaffold Protein Homer1b/c Links Metabotropic Glutamate Receptor 5 to Extracellular Signal-Regulated Protein Kinase Cascades in Neurons.
L. Mao, L. Yang, Q. Tang, S. Samdani, G. Zhang, and J. Q. Wang (2005)
J. Neurosci. 25, 2741-2752
   Abstract »    Full Text »    PDF »
Displacement of SATB1-Bound Histone Deacetylase 1 Corepressor by the Human Immunodeficiency Virus Type 1 Transactivator Induces Expression of Interleukin-2 and Its Receptor in T Cells.
P. P. Kumar, P. K. Purbey, D. S. Ravi, D. Mitra, and S. Galande (2005)
Mol. Cell. Biol. 25, 1620-1633
   Abstract »    Full Text »    PDF »


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