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Adriana Avila Flores

Potential speakers for pharma meetings-Adriana Avila Flores

Title: Branched amphiphilic cationic oligo-peptides for delivery of HPV-16 DNA vaccines

Adriana Avila Flores

Auburn University, USA

Biography

I completed my Ph.D. in Biochemistry and Molecular Biophysics at Kansas State University. My thesis work focused on developing a method to deliver genes into cells using peptide nano-spheres. Previously, I helped to establish a biotechnology company, Genetadi Biotech SL, in Bilbao, Spain and also worked at the R & D department of the company from 2008 to 2010. Currently I am a research associate at Auburn University working in the field of drug delivery and microfluidics and also serving as a co-chair for the Gordon Research Seminar in Cancer Nanotechnology.

Abstract

Peptide vesicles are emerging as an alternative gene delivery approach over lipid-based methods, featuring resistance to oxidation and thermal stability. Additionally, peptides are easy to synthesize, quite stable and expected to produce minimally immunogenic and inflammatory responses. We recently reported on a new class of branched amphiphilic peptides that self-assemble into extremely stable nano-spheres. The Branched Amphiphilic Peptides Capsules (BAPCs) display a uniform size of 20-30 nm and are resistant to detergents, proteases and chaotropes. Comparable to how histones compact DNA to form nucleosomes, the 20- 30 nm BAPCs interact with plasmid DNA acting as a cationic nucleation centers with the negatively charged DNA coating the outer surface. The BAPCs-DNA nanoparticles are capable of delivering plasmid DNA of different size into cells in culture, yielding high transfection rates and minimal cytotoxicity. HeLa cells transfected with the BAPCs-DNA complexes showed transfection rates approaching 55 % (higher than cells treated with Lipofectin®). After evaluating the transfection efficiency and toxicity of the DNA-coated BAPCs in vitro, we tested the nano-sized complexes ability to deliver DNA in vivo. For that purpose, we tested a DNA vaccine that encodes the HPV-16 E7 oncoprotein (pgDE7). Mice immunized with pgDE7-coated BAPCs managed to constrain tumor growth up to one month after transplantation of the TC-1 cells. In addition, the survival time was enhanced by two-fold in comparison to that observed in the non-complexed DNA group. The DNA-loaded BAPCs, at the most effective in vivo concentration, showed no detectable toxic effects, as evaluated by some critical tissue injury biomarkers. These results indicate that the complexation of plasmid DNA to nano-sized BAPCs represents a promising non-viral gene delivery approach for in vitro transfection of mammalian cells and for the in vivo activation of immune responses.

Audience will learn:
About a versatile and biocompatible peptide-base nanomaterial with potential applications in DNA vaccine delivery.
I will present cutting edge methods followed for the biophysical characterization of the peptide capsules.