Intracellular Protein Therapy with TSDT
Protein transduction exploits the ability of specific basic-, amphipathic- and hydrophobic- cell penetrating peptide (CPP) sequences to enhance the uptake of proteins and other macromolecules by mammalian cells.
We previously developed hydrophobic CPPs, named macromolecule transduction domains (MTDs) derived from the hydrophobic (H) regions of signal sequences (HRSSs) to deliver biologically active peptides and proteins into a variety of cells and tissues.
By using the MTD, recombinant cell-permeable (CP-) proteins fused to MTDs to deliver therapeutically active cargo proteins into cancer cells were developed to regulate cell cycle. However, the recombinant proteins including CP-Proteins expressed in bacteria system were hard to be purified as soluble form due to their low solubility and yield.
To address the crucial weakness for further clinical development of the CP-Proteins as protein-based biotherapeutics, advanced form (aMTD) of the CPP has newly been developed through critical factors-based peptide analysis.
In the Cellivery, we have demonstrated that TSDT enabled by the novel hydrophobic CPPs – aMTDs may provide novel protein therapies against cancer and other diseases.