Maria Pelliccia

First name
Maria
Last name
Pelliccia
Year of Study
Thesis Title
Strategies for enhancing viral gene transfer and the thermostability of viral vectors in vaccine applications
Thesis Abstract
Viruses represent powerful gene delivery systems in biomedicine. For successful gene therapy and immunization programs, the efficiency and stability of viral vectors are fundamental aspects (Jorio et al. 2006). To address this challenge, in the present project we investigated the interaction between viruses and nanomaterials. We tested three types of sulfonate- functionalized gold nanoparticles (AuNPs), MUS:OT, MUS and MUS:brOT NPs, which are small than 5 nm, negatively charged and poorly cytotoxic (Verma et al. 2008). As virus models we focused on human recombinant adenovirus type 5 (Ad) and on two enteroviruses, echovirus-1 (EV1) and coxsackievirus B3 (CVB3). We carried out two sets of experiments: (1) Short-term pretreatment of Ad with nanomaterials for 1 h at 37°C that showed a significant increase in the gene expression in vitro and in vivo. The NPs- enhanced adenovirus transduction aims to reduce Ad vector doses in vivo in order to minimize the adverse reactions of the immune response due to high vector dosage. (2) Long-term thermostabilization studies of Ad, EV1 and CVB3 in vitro in the presence of nanomaterials and other compounds such as sugars at 37°C or room temperature for extensive periods of time. Nanomaterials and sucrose increased substantially the heat stability of viruses. To elucidate the thermal inactivation mechanism of viruses and the stabilizing effect observed, we developed an analytical theory. This research fits in the context of developing more thermo-stable preparations for vaccine that do not require the challenging cold chain in order to preserve the effectiveness of viral vaccines.
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