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Tat-mediated delivery of heterologous proteins into cells.
Open accessAbstract
The Tat protein of human immunodeficiency virus 1 (HIV-1) can enter cells efficiently when added exogenously in tissue culture. To assess if Tat can carry other molecules into cells, we chemically cross-linked Tat peptides (residues 1-72 or 37-72) to beta-galactosidase, horseradish peroxidase, RNase A, and domain III of Pseudomonas exotoxin A (PE) and monitored uptake colorimetrically or by cytotoxicity. The Tat chimeras were effective on all cell types tested, with staining showing uptake into all cells in each experiment. In mice, treatment with Tat-beta-galactosidase chimeras resulted in delivery to several tissues, with high levels in heart, liver, and spleen, low-to-moderate levels in lung and skeletal muscle, and little or no activity in kidney and brain. The primary target within these tissues was the cells surrounding the blood vessels, suggesting endothelial cells, Kupffer cells, and/or splenic macrophages. Tat-mediated uptake may allow the therapeutic delivery of macromolecules previously thought to be impermeable to living cells.
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Cited by
Vivès, E., Brodin, P., & Lebleu, B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.25.16010 · Cited by 2,373
Wadia, J. S., Stan, R. V., & Dowdy, S. F. (2004) · Nature Medicine · doi:10.1038/nm996 · Cited by 1,647
Activation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix
Walensky, L. D., Kung, A. L., Escher, I., Malia, T. J., Barbuto, S., Wright, R. D., Wagner, G., Verdine, G. L., & Korsmeyer, S. J. (2004) · Science · doi:10.1126/science.1099191 · Cited by 1,349
Mahley, R. W., Weisgraber, K. H., & Huang, Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600549103 · Cited by 912
Getting Across the Cell Membrane: An Overview for Small Molecules, Peptides, and Proteins
Yang, N. J., & Hinner, M. J. (2015) · Methods in Molecular Biology · doi:10.1007/978-1-4939-2272-7_3 · Cited by 826
Metadata
- Authors
- Fawell, S., Seery, J., Daikh, Y., Moore, C., Chen, L. L., Pepinsky, B., & Barsoum, J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1994-01-18
- Volume
- 91
- Issue
- 2
- Pages
- 664-668
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2001582257
- Cited by
- 1,225
- References
- 0
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- green
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- Fawell, S., Seery, J., Daikh, Y., Moore, C., Chen, L. L., Pepinsky, B., & Barsoum, J. (1994). Tat-mediated delivery of heterologous proteins into cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.91.2.664
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