Delivery of Non-Native Cargo into Mammalian Cells Using Anthrax Lethal Toxin.

The intracellular delivery of peptide and protein therapeutics is a major challenge due to the plasma membrane, which acts as a barrier between the extracellular environment and the intracellular milieu. Over the past two decades, a nontoxic PA/LFN delivery platform derived from anthrax lethal toxin has been developed for the transport of non-native cargo into the cytosol of cells in order to understand the translocation process through a protective antigen (PA) pore and to probe intracellular biological functions. Enzyme-mediated ligation using sortase A and native chemical ligation are two facile methods used to synthesize these non-native conjugates, inaccessible by recombinant technology.