Rational Engineering of Cytosolic Delivery Systems for Protein Therapeutics

Protein therapeutics holds enormous promise for the treatment of various diseases but is limited to extracellular targets because of the membrane impermeable nature of most proteins. Cytosolic protein delivery systems are of great importance in the development of next-generation protein therapeutics. Since proteins are biomacromolecules characterized with limited binding sites, chemical modification or genetic engineering of cargo proteins is usually required to strengthen their binding affinity with the delivery carriers, which, however, may irreversibly impair their bioactivities. As thus, protein delivery systems that can efficiently transport native proteins into the cytosol of living cells with uncompromised bioactivities are highly desired.