Protein replacement by receptor-mediated endocytosis corrects the sensitivity of Fanconi anemia group C cells to mitomycin C

Current methods for direct gene transfer into hematopoietic cells are ineff icient. Here we show that functional complementation of Fanconi anemia (FA) group C cells by protein replacement can be as efficacious as by transfect ion with wild-type FAC cDNA, We expressed a chimeric protein (called His-IL FAC) consisting of the mature coding portion of gibbon interleukin-3 (IL-3) and full-length FAC in Escherichia coli, The purified bacterial protein is internalized by hematopoietic cells via IL-3 receptors. The intracellular half-life of His-ILFAC is approximately 60 minutes, which is comparable to that of the transgene-encoded FAC protein. In this cell-culture model His-I LFAC completely corrects the sensitivity of FA group C cells to mitomycin C , but it has no effect on FA cells that belong to complementation groups A and B, We suggest that receptor-mediated endocytosis of cytokine-fusion pro teins may be of general use to deliver macromolecules into hematopoietic pr ogenitor cells. (C) 1999 by The American Society of Hematology.