THE EFFECTS OF HUMAN SERUM AND CEREBROSPINAL-FLUID ON RETROVIRAL VECTORS AND PACKAGING CELL-LINES

Human serum is known to inactivate many retroviruses, including murine leukemia viruses (MLV). Exposure of vectors based on MLV to human serum components would presumably decrease the efficiency of gene transfer in vivo. Human serum also lyses xenogeneic cells, which would affect the survival of retroviral vector packaging cells in vivo. The effects of other body fluids, such as cerebrospinal fluid (CSF), on MLV vectors and packaging lines have not been studied. We have found that retroviral vectors packaged in ecotropic, amphotropic, and gibbon ape leukemia virus (GALV) envelope proteins were all inactivated by human sera, and human sera also lysed mouse NIH-3T3 cells and the retroviral vector packaging cells derived from them. Human fibroblasts producing amphotropic vector particles were resistant to lysis, but the particles produced by them were inactivated. In contrast, CSF did not inactivate MLV vectors, nor did it lyse murine retrovirus packaging cells. Our results suggest that exposure to human serum may prevent in vivo gene transfer by MLV vectors and xenogeneic packaging lines, but gene transfer within the central nervous system should be more successful.