Selective virus-mediated intracellular delivery of membrane-impermeant compounds by means of plasma membrane vesicles

The impermeability of the cell plasma membrane is a major obstacle to intracellular delivery of large hydrophilic molecules, such as many kinds of drugs. This contribution describes a general-purpose delivery system that employs the membrane fusion capacity of enveloped viruses to circumvent cell impermeability. Vesicles were generated from the plasma membrane of HEp-2 cells, a human cell line host for the Newcastle disease virus (NDV). They could be loaded with a fluorescent, high molecular weight dye (FITC/dextran, MW 70 KDa) or with the enzyme ribonuclease A (MW 14 KDa). These vesicles were found to fuse and deliver their lumen contents to cultured HEp-2 cells in the presence of NDV virions. When ribonuclease was employed as the encapsulated solute, viral replication was inhibited and death of the infected cells was accelerated. Implications and possible applications of this technique in antiviral therapy are discussed.