Cell-Specific Delivery of Bacteriophage-Encapsidated Ricin a Chain

We have used covalent coupling of deglycosylated ricin A chain (RAC) to the assembly initiation/translational repression RNA stem-loop (TR) of the bacteriophage MS2 to direct encapsidation of the toxin in bacteriophage capsids. Multiple copies of the TR-RAC conjugate can be incorporated into single capsid shells. The resultant particles can then be directed to specific cells by receptor-mediated endocytosis (RME) of complexes formed with anti-MS2 coat protein antibodies or by further covalent modification of the capsids by addition of human transferrin molecules. The results suggest that bacteriophage encapsidation and targeting is an efficient way to deliver toxins in a cell-specific fashion. The system may have widespread application in the field of targeted drug delivery, including antisense reagents.