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

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L A Avila, L R M M Aps, M O Diniz, L C S Ferreira and J M Tomich

Auburn University, USA
University of Sao Paulo, Brazil
Kansas State University, USA

: J Pharm Drug Deliv Res

Abstract

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Recently, peptides have shown potential as a new family for gene carriers. 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, generating peptide-DNA nanoparticles with sizes ranging between 50-250 nm. The BAPCs-DNA nanoparticles are capable of delivering plasmid DNA of different size into cells in culture, yielding high transfection rates and minimal cytotoxicity. Furthermore, BAPCs were tested for in vivo delivery of a DNA vaccine previously designed to activate immune responses and capable of controlling tumors induced by type 16 human papillomavirus (HPV-16). The BAPCs-DNA nanoparticles enhanced the vaccine-induced antitumor protection and promoted efficient activation of murine dendritic cells without significant toxic effects. Together these results demonstrate that the interaction of double stranded DNA to branched amphiphilic oligo-peptides nanoparticles represents a promising new in vitro and in vivo non-viral gene delivery system.

Biography

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L A Avila has completed her PhD in Biochemistry and Molecular Biophysics at Kansas State University in 4 years. Her thesis work focused on developing a method to deliver genes into cells using peptide nano-spheres. Currently, she is a Research Associate at Auburn University working in the field of drug delivery and microfluidics. She has helped to establish a biotechnology company, Genetadi Biotech SL, in Bilbao, Spain from 2008 to 2010 and she had been a founding partner since then. She has published 5 research papers and 1 review article. Presently, she is serving as a co-chair for the Gordon Research Seminar in Cancer Nanotechnology.

Email: adriana.avila@auburn.edu