Bacterial toxins as versatile delivery vehicles

An ability to deliver macromolecules into the intracellular compartments Of mammalian cells offers enormous potential for development of new therapeutics directed against intracellular targets. Unfortunately, most peptides or proteins are too large to enter the cell cytosol unaided, and any uptake that does occur primarily results in their entry into lysosomes for degradation. However, one group of proteins that possesses an inherent capacity to interact with and enter mammalian cells are bacterial toxins. These are being developed as efficient vehicles for the attachment and intracellular delivery of other macromolecules, including peptides, proteins and DNA. To date, most studies have concentrated on the delivery of immunological epitopes into the endogenous major histocompatibility class I (MHC-I) pathway for development of antiviral or anticancer vaccines. However, opportunities to use toxins to modulate inflammatory autoimmune disorders and cell-specific targeting of DNA for gene therapy illustrates the versatility of toxin molecules as delivery vehicles.