Immunospecific vesicle targeting facilitates fusion with selected cell populations

Antibody-directed targeting of vesicles to cells dramatically enhances polyethylene glycol-mediated fusion and microinjection. Sealed erythrocyte ghosts or liposomes, containing fluorescent bovine serum albumin, were targeted to murine spleen and thymus cells, and to lymphocyte and monocyte cell lines. In all cases, targeted cell populations showed substantial levels of microinjection, whereas populations treated with the fusogen in the absence of targeting were not significantly microinjected. Attachment of vesicles to selected cells was achieved by first labelling the cells with biotin-modified antibody and then treating them with avidin-coupled sealed ghosts or liposomes. Another approach to the promotion of selective fusion aims to alter the cell recognition properties of Sendai virus so that its fusogenic activity may be redirected to specific cellular targets. The agglutination and fusion of red cells by UV-inactivated Sendai virus were completely blocked by low concentrations of a Fab preparation of a monoclonal antibody against the viral haemagglutinin (HN) sites. Agglutination and fusion activity were restored in the presence of Fab-anti-HN by providing an alternative recognition system, namely, when the virus had been coupled with biotin and the red cells with avidin. Methods for facilitating microinjection by specifically directing vesicles to target cells may be particularly useful in overcoming barriers to the transfer of genes into lymphocytes by standard transfection techniques.