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Cell-penetrating peptides: 20 years later, where do we stand?

Twenty years ago, the discovery of peptides able to cross cellular membranes launched a novel field
in molecular delivery based on these non-invasive vectors, most commonly called cell-penetrating
peptides (CPPs) or protein transduction domains (PTDs). These peptides were shown to efficiently
transport various biologically active molecules inside living cells, and thus are considered promising
devices for medical and biotechnological developments. Moreover, CPPs emerged as potential tools
to study the prime mechanisms of cellular entry across the plasma membrane. This review is ded-
icated to CPP fundamentals, with an emphasis on the molecular requirements and mechanism of
their entry into eukaryotic cells.

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