Redirected infection of directly biotinylated recombinant adenovirus vectors through cell surface receptors and antigens

The inability of adenovirus to infect primitive hematopoietic cells present s an obstacle to the use of adenovirus vectors for gene transfer to these c ell types. Therefore, expanding the tropism of adenovirus vectors to unique cell surface antigens would be an important development for gene therapy p rotocols, In this study, we sought to redirect infection of adenovirus vect ors to primitive human hematopoietic cells that universally express the c-K it receptor on their cell surface. To accomplish this, a vector was constru cted by covalently linking biotin molecules to recombinant adenovirus, foll owed by addition of the biotinylated ligand for the c-Kit receptor, stem ce ll factor (SCF), through an avidin bridge. Gene transfer was directed speci fically to c-Kit-positive hematopoietic cell lines, resulting in up to a 2, 440 fold increase in luciferase expression with frequencies equivalent to r ecombinant virus infection of permissive cells. Substitution of biotinylate d antibodies directed against c-Kit, CD34 (binds L-selectin), and CD44 (hya luronate receptor) receptors for biotinylated SCP resulted in 50-, 8-, and 260-fold increases in reporter gene expression, respectively, demonstrating that infection also could be redirected through antibody-antigen interacti ons and through antigens other than growth factor receptors, The versatilit y of this vector was demonstrated further by infection of primary T cells w ith vectors targeted with antibodies to CD44 (resting and activated T cells ) and biotinylated IL-2 (activated T cells only). Taken together, directly biotinylated adenovirus vectors represent a versatile and efficient method for redirection of virus infection to specific cells.