A New Approach to the Development of an RSV Anti-viral Targeted Nanocarrier for Dual Inhibition of Viral Infection and Replication
Master of Science (M.S.)
Degree Granting Department
Shyam Mohapatra, Ph.D.
Yashwant Pathak, Ph.D.
Daniel Denmark, Ph.D.
Nanoparticles, Nanotechnology, RNA Interference, Transfection
Respiratory Syncytial Virus (RSV) is a potentially life-threatening respiratory pathogen that infects approximately 64 million children and immunocompromised adults globally per year. Currently, there is a need for prophylactic and therapeutic approaches effective against primary and secondary RSV infections. This project focuses on the development of a simple, smart, and scalable anti-RSV nanotherapeutic that combines novel cellular antiviral defense mechanisms targeting the inhibition of viral fusion and replication. An ICAM-1 targeted liposomal nanocarrier will be synthesized and coated with a layer of chitosan containing the anti-fusion HR2-D peptide as an extracellular defense mechanism. Additionally, chitosan complexed to dual expressing short hairpin RNA (shRNA) recombinant plasmids will be encapsulated within the nanocarrier, and provide an intracellular defense mechanism that will interfere with the expression of the NS1 and P proteins. In combination, both defense mechanisms are expected to induce a synergistic anti-RSV effect that will surpass those of conventional therapeutics. Through this research, the NS1 and P containing plasmid (pSH-NS1-P) was cloned, and the nanotherapeutic was successfully synthesized. Based on the acquired results, pSH-NS1-P was shown to express anti-RSV effects, and it was also concluded that both inserts were producing active shRNA. Additionally, the anti-RSV efficiency of HR2-D was confirmed. Overall, this research will lead to development of a dual-mechanistic anti-viral nanotherapeutic.
Scholar Commons Citation
Singer, Anthony N., "A New Approach to the Development of an RSV Anti-viral Targeted Nanocarrier for Dual Inhibition of Viral Infection and Replication" (2018). USF Tampa Graduate Theses and Dissertations.