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Drug and Gene Targeting
Efficient Delivery of Agents to Molecular Targets
The example below demonstrates the feasibility of delivering an agent, in this case a
mutant form of diptheria toxin, to the endothelial cell surface by a carbohydrate, sLea,
conjugated to the toxin. The toxin, CRM107 is a mutant form of diptheria toxin in which a
point mutation has been introduced in the cell binding site to reduce the toxicity
10,000-fold compared to the wild type toxin. Conjugating the carbohydrate, sLea, which
recognizes E-selectin on the endothelial cell surface, to CRM107 restores the toxicity as
seen in the results of the assay below. Within one hour, most of the endothelial cells
have been killed which is in direct contrast to the unconjugated toxin which does not
result in any observed killing within one hour of flow. The use of direct coupling of a
carbohydrate to an agent to improve the efficiency of delivery would have application in
drug, gene, and cell therapies.