Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
8R01EB000252-07
Application #
6519703
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Moy, Peter
Project Start
1996-02-01
Project End
2003-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
7
Fiscal Year
2002
Total Cost
$274,515
Indirect Cost

  Institution

Name
University of Washington
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Jastrzebska, Katarzyna; Florczak, Anna; Kucharczyk, Kamil et al. (2018) Delivery of chemotherapeutics using spheres made of bioengineered spider silks derived from MaSp1 and MaSp2 proteins. Nanomedicine (Lond) 13:439-454
Hoffman, John M; Stayton, Patrick S; Hoffman, Allan S et al. (2015) Stimuli-responsive reagent system for enabling microfluidic immunoassays with biomarker purification and enrichment. Bioconjug Chem 26:29-38
Jose, Rod R; Elia, Roberto; Tien, Lee W et al. (2014) Electroresponsive aqueous silk protein as ""smart"" mechanical damping fluid. ACS Appl Mater Interfaces 6:6212-6
Omura, Tomoyuki; Ebara, Mitsuhiro; Lai, James J et al. (2014) Design of smart nanogels that respond to physiologically relevant pH values and temperatures. J Nanosci Nanotechnol 14:2557-62
Ebara, Mitsuhiro; Hoffman, John M; Hoffman, Allan S et al. (2013) A photoinduced nanoparticle separation in microchannels via pH-sensitive surface traps. Langmuir 29:5388-93
Nash, Michael A; Waitumbi, John N; Hoffman, Allan S et al. (2012) Multiplexed enrichment and detection of malarial biomarkers using a stimuli-responsive iron oxide and gold nanoparticle reagent system. ACS Nano 6:6776-85
Fridley, Gina E; Le, Huy Q; Fu, Elain et al. (2012) Controlled release of dry reagents in porous media for tunable temporal and spatial distribution upon rehydration. Lab Chip 12:4321-7
Kinahan, Michelle E; Filippidi, Emmanouela; Koster, Sarah et al. (2011) Tunable silk: using microfluidics to fabricate silk fibers with controllable properties. Biomacromolecules 12:1504-11
Landesberg, Regina; Woo, Victoria; Cremers, Serge et al. (2011) Potential pathophysiological mechanisms in osteonecrosis of the jaw. Ann N Y Acad Sci 1218:62-79
Kirk, James T; Fridley, Gina E; Chamberlain, Jeffrey W et al. (2011) Multiplexed inkjet functionalization of silicon photonic biosensors. Lab Chip 11:1372-7

Showing the most recent 10 out of 28 publications