Targeting Vector
In a viral vector, a section of the envelope protein gene is replaced by the coding sequences of, e.g., 150-amino acids of erythropoietin (EPO) and thus, the replacement improves its ability to recognize the EPO receptor. Other approaches involve pseudotyping or attaching special ligands to the envelope (Müller OJ et al 2003 Nature Biotechnol 21:1040). Liposomal vehicles may be conjugated with special antibodies for target recognition. Bifunctional antibodies that recognize both viral epitopes and target cell antigens have been constructed. Another approach was found to covalently link biotin to recombinant adenovirus. The Kit receptor and the stem cell factor (SCF) were then linked through an avidin bridge to the target to assure the proper tropism. It is highly desirable that ligand–receptor pairs be limited to specific functions rather than cross over to members of regulatory networks. Such a goal can be reached by stepwise, individual, site-specific saturation mutagenesis followed by phenotypic screening based on the yeast two-hybrid system. The nuclear hormone estrogen receptor so modified can favor a synthetic 4,4′-dihydroxybenzil by more than a million-fold over the natural ligand 17 β-estradiol. Such a technique can specifically target human endometrial cancer (Chockalingam K et al 2005 Proc Natl Acad Sci USA 102:5691). liposome, vectors, pseudotyping, magic bullet, gene therapy, KIT oncogene, stem cell factor, biotin, avidin, epitope, dihydoxybenzil, nuclear receptor, estradiol, estrogen receptor, targeting transcriptional; Peng KW et al 2001 Gene Ther 8:1456; Yu D et al 2001 Cancer Gene Ther 8:628; therapeutic applications: Waehler R et al 2007 Nature Rev Genet 8:573.