from the feldan site...THE FELDAN SHUTTLE...

from the feldan site...

THE FELDAN SHUTTLE TECHNOLOGY

Cell-Penetrating Peptides as Intrabody CarriersUsing short protein domains as intracellular carriers is a strategy discovered in 1965 that was rationally considered 30 years ago after the identification of the first cell-penetrating peptide (CPP), isolated from the HIV-transactivator TAT.^15,16 Actually, several CPPs have been identified and fused to proteins to mediate their intracellular delivery. However, CPPs mediate intracellular uptake through endocytic processes that lead to the sequestration and the enzymatic degradation of proteins into vesicular compartments, named endosomes, that substantially reduces the likelihood to get functional effect.¹⁷

The Endosomal Escape StrategyIndeed, the endosomal escape of delivered proteins is a challenging and limiting step that requires endosome destabilizing strategies.¹⁸ To overcome this hurdle, peptides with endosomal leakage properties could promote the cytosolic release of biomolecules from endosomes.^19,20 These peptides, named endosomal leakage domains (ELDs), are unable to deliver proteins in cells on their own. Indeed, using both CPPs and ELDs could be an approach resulting in a peptide with both protein uptake and endosomal escape properties (Figure 1). Recently, the fusion of CPPs with ELDs was validated as a promising peptide-based delivery strategy with easily adaptable protocols for macromolecule delivery that provided exciting results into mammalian cells.^21-23 These investigations encouraged us to deepen our understanding of the biochemical and structural properties required for the design of peptides mediating the efficient and safe delivery of proteins into mammalian cells.

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