Tuesday, October 27, 2015
1:00 pm, MRB 202
Dr. John Tomich
Department of Biochemistry and Molecular Biophysics Kansas State University
Branched Amphipathic Peptide Bilayers: A Singularly Versatile Biomaterial
Our lab has developed peptide bilayer delimited nano-capsules through the facile and rapid co-assembly of two branched amphiphilic peptides: bis(FLIVIGSII)-K-K4 and bis(FLIVI)-K-K4. The Branched Amphiphilic Peptides (BAPs) assemble into Capsules (BAPCs) that possess unusual but highly desirable properties that suggest transformative applications in medicine and industry. Their size can be controlled from 20 nm to over 1 micron depending on annealing conditions. They are resistant to heat, detergents, proteases, osmotic pressure, chaotropes, thermal neutrons, the recoil of alpha-emitting radionuclides and the cell’s degradative machinery. This stability currently limits use for the delivery and release of encapsulated cargo. However, they are ideally suited for entrapping, targeting, delivering and retaining radioactive molecules for radiotherapy. In vivo results revealed an alter biodistribution compared to expose to the free salt. In addition to radiation therapy the BAPCs can deliver DNA/RNA nucleotides that bind to the cationic outer-surface of these structures with negligible cytotoxicity. Many current DNA delivery methodologies function well in vitro but are too toxic for in vivo applications. The DNA-histone like complexes yield transfection rates in mammalian cells of up to 75% for a 5 kb plasmid and 35% for a 20kb plasmid. with minimal cytotoxicity. An in vivo DNA vaccine study was performed using a 4.7 kb plasmid encoding the E7 oncoprotein of HPV-16. It stimulated both immune and inflammatory responses, again with minimal organ toxicity. More recently this same system was able to deliver to primate cells in culture a 20 kb plasmid containing a cDNA that coded for an attenuated corona virus. The delivery of this vector resulted in the shedding of live attenuated virus.