Page 3 Drug and Gene Targeting Efficient Delivery of Agents to Molecular Targets The targeting flow assay uses a flow loop we designed to allow continuous circulation of the glycoconjugate in solution over the cellular monolayer. This allows targeting to be observed under dynamic conditions as would occur in vivo in the vascular system. The cell monolayer can be observed, usually under epifluorescence, during the course of the assay to monitor the time dependent effects of the glycoconjugate delivery of agents to the cell surface. The schematic of the flow loop apparatus is shown below. Development of Targeting The strategy for development of targeting into a viable technology is to conceptualize targeting as comprised of two events for research investigation. The first event is the delivery and binding of the targeted agent to the cell surface. This event of recognition is relevant to applications of diagnostic imaging and drug delivery schemes in which the site of action of the drug is extracellular. The second event, subsequent to the first, is the effect on the cell of the targeted agent. The efficiency of the second event is critical for drugs which need to be internalized to reach their intracellular targets and in gene therapy for which the gene must be taken up by the cell and expression of the therapeutic protein is required for clinical success. Targeting formats which should be investigated as delivery vehicles include direct coupling of carbohydrate to the drug, polymers and dendimers linked with carbohydrates, and liposomes. Each one of these delivery vehicles may have