The specific aims of this competitive renewal proposal are to develop stimuli-responsive bioconjugates and complexes as molecular switches for controlling (a) biorecognition processes (""""""""bioactivity switches"""""""") and (b) intracellular trafficking of biomolecules (""""""""membrane switches""""""""). Bioactivity switches are responsive polymer-engineered protein (RP-EP) conjugates that can be stimulated to turn protein activity on and off , or trigger release of bound ligand. Applications as on-off switches include affinity separations, diagnostics, drug targeting, and enzyme processes, such as PCR, industrial enzyme processes and detergent and fabric finishing processes. Actions of bioactivity switches as triggered release systems include the delivery of: biotinylated agents, affinity biomolecules, drugs, chemical agents, enzyme substrates, products or inhibitors, and signals. Such actions have many diverse uses in medicine, biotechnology and industry. Membrane switches are pH-responsive polymer bioconjugates or complexes with drug carriers that disrupt endosomal membranes to enhance intracellular delivery of DNA or protein drugs. This action should increase the efficacies of gene, antisense oligonucleotide, and cancer therapies.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Lewis, Catherine D
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University of Washington
Biomedical Engineering
Schools of Engineering
United States
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Cheung, Charles Y; Stayton, Patrick S; Hoffman, Allan S (2005) Poly(propylacrylic acid)-mediated serum stabilization of cationic lipoplexes. J Biomater Sci Polym Ed 16:163-79
Stayton, Patrick S; Ding, Zhongli; Hoffman, Allan S (2004) Smart polymer-streptavidin conjugates. Methods Mol Biol 283:37-43
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