STRATEGIES TO ACHIEVE TARGETED GENE DELIVERY VIA THE RECEPTOR-MEDIATED ENDOCYTOSIS PATHWAY

Gene transfer to eukaryotic cells may be accomplished by capitalizing on endogenous cellular pathways of macromolecular transport. In this r egard, molecular conjugate vectors have been developed which deliver D NA via the receptor-mediated endocytosis pathway. An attractive featur e of this vector system is the potential to achieve targeted gene deli very based upon flexible incorporation of a targeting ligand. In this review we describe steps that have been taken to optimize this vector system. Specific strategies include the incorporation of mechanisms to achieve conjugate escape from the endosome and the derivation of meth ods to eliminate sources of nonspecificity. These developments have de monstrated the potential to construct a vector system in which multipl e independent components may function in a concerted manner to accompl ish targeted high efficiency gene delivery. In their present state of development, molecular conjugate vectors may have many potential appli cations for in vitro use.