| 摘要 |
Disclosed is a receptor-mediated protein delivery system using a ligand derived from the Region II of malarial circumsporozoite (CS) protein which recognizes receptors specifically localized on the surface of liver cells in vivo and many types of cultured cells grown in vitro. Using the present invention, a "suicidal gene product", cytosine deaminase, has been successfully fused to CS protein. The recombinant fusion protein possesses both cell type targeting specificity of CS as well as cytosine deaminase enzymatic activity which catalyzes the conversion of prodrug 5-fluorocytosine into antitumor drug 5-fluorouracil and elicit cell killing capacity. Moreover, the fusion protein exhibits prolonged stability and sustained cell killing activity, due to the entrapment of the recombinant protein in a particular cellular (most likely endosome-lysosomal) compartment. Thus, the present invention provides technology for improved cell-type specificity and enhanced favorable pharmacokinetics of drug delivery.
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