Protein transduction domain delivery of therapeutic macromolecules |
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Authors: | van den Berg Arjen Dowdy Steven F |
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Institution: | Howard Hughes Medical Institute, Department of Cellular & Molecular Medicine, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0686, United States |
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Abstract: | Owing to their unprecedented selectivity, specific activity and potential for 1000+ fold amplification of signal, macromolecules, such as peptides, catalytic protein domains, complete proteins, and oligonucleotides, offer great potential as therapeutic molecules. However, therapeutic use of macromolecules is limited by their poor penetration in tissues and their inability to cross the cellular membrane. The discovery of small cationic peptides that cross the membrane, called Protein Transduction Domains (PTDs) or Cell Penetrating Peptides (CPPs), in the late 1980s opened the door to cellular delivery of large, bioactive molecules. Now, PTDs are widely used as research tools, and impressively, multiple clinical trials are testing PTD-mediated delivery of macromolecular drug conjugates in patients with a variety of diseases. |
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