Journal
JOURNAL OF CONTROLLED RELEASE
Volume 89, Issue 3, Pages 499-511Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0168-3659(03)00150-0
Keywords
targeted delivery; assembled targeting complexes; vascular endothelial growth factor; human RNase; gene therapy
Funding
- NHLBI NIH HHS [2R44 HL6143-02] Funding Source: Medline
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Targeted drug delivery requires loading' drugs onto targeting proteins. Traditional technologies for loading drugs rely on I chemical conjugation of drugs or drug carriers to targeting proteins. An alternative approach might rely on assembly of targeting complexes using a docking system that includes two components: a 'docking' tag fused to a targeting protein, and a 'payload' module containing an adapter protein for non-covalent binding to the docking tag. We describe here a fully humanized adapter/docking tag system based on non-covalent interaction between two fragments of human pancreatic RNase I. A 15 amino acid long N-terminal fragment of RNase I designed to serve as a docking tag, was fused to the N-terminus of human vascular endothelial growth factor that served as a targeting protein. An 18-125 and an 18-127 amino acid long fragments of RNase I were engineered, expressed and refolded into active conformations to serve as adapter proteins. Interactions between the targeting and adapter proteins were characterized using enzymatic analysis and surface plasmon resonance. Targeting DNA delivery complexes were assembled, characterized by dynamic light scattering, and found to be very effective in receptor-mediated DNA delivery. (C) 2003 Elsevier Science B.V. All rights reserved.
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