Protein transduction

Protein transduction refers to the biological process and delivery mechanism by which exogenous proteins, peptides, and other macromolecules are internalized into cells from the extracellular environment (Schwarze et al., 1999, Science). This phenomenon is typically mediated by short, often cationic or amphipathic sequences known as Protein Transduction Domains (PTDs) or Cell-Penetrating Peptides (CPPs), such as the HIV-1 TAT peptide or the Antennapedia-derived penetratin (Ford et al., 2001, Gene Therapy). Unlike discrete molecular entities like receptors or enzymes, protein transduction is an internalization pathway and is not considered a specific therapeutic target for drug inhibition or activation (Bechara & Grimaldi, 2013, FEBS Letters). In biotechnology, this process is exploited as a delivery strategy to transport functional proteins—such as transcription factors, enzymes for replacement therapy, and gene-editing tools—directly to their intracellular sites of action (Guidotti et al., 2017, Trends in Pharmacological Sciences). However, the clinical utility of protein transduction is currently challenged by a lack of tissue specificity and the tendency of cargo to become trapped within endocytic vesicles (Erazo-Oliveras et al., 2012, Pharmaceuticals). Consequently, the term describes a method of therapeutic delivery rather than a standalone molecular target.

Other names

Protein deliveryProtein internalizationPTD-mediated uptakeCell-penetrating peptide transductionMembrane translocation of proteins

Utilization of protein transduction domains (PTDs) or cell-penetrating peptides (CPPs) to facilitate the crossing of biological membranes by macromolecules via macropinocytosis or direct membrane penetration.