Smart bioconjugates

Many bioengineering technologies depend on communication between devices and cells or biomolecules. Effective communication in the device environment is based on controlling recognition events at the device interface. we are developing strategies to introduce "listening" capabilities into bioengineering technologies that provide sensitive and reversible control over biomolecular recognition events. Our approach utilizes "smart" polymers that can be used as molecular switches controlling (a) biorecognition processes (bioactivity switches) and(b) intracellular trafficking of biomolecules (membrane switches). Bioactivity switches are responsive polymer-engineered protein 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. 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. 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.