Using QB VLPS to package, protect, and deliver in vivo produced RNAS

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Fang, Po-Yu
Hud, Nicholas V.
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This project focuses on Using Qβ VLPs to package, protect, and deliver recombinantly produced RNAs. The ultimate goal is to develop an RNA interference (RNAi) delivery platform to inhibit gene expression that is spontaneously assembling and scalable for potential medical applications. Preliminary studies suggested that this platform is amenable to efficient packaging of functional RNA and, most recently, simultaneous packaging with DNA plasmid. The principle goals were to i) determine the prevailing factors that affect efficient RNA assembly within VLPs, ii) demonstrate spontaneously intracellular uptake of VLP-cargos, iii) design a RNAi scaffold for one step in vivo VLP-RNA assembly, iv) deliver VLP-RNAi to human cancer cells for gene knockdown and expression, and vi) decorate RNA-containing VLP with polymer for plasmid delivery. The ultimate goal is to deliver multifunctional VLPs against brain tumor growth in mice. The new RNAi scaffold we designe can carry different target siRNAs and self-assemble into stable RNA nanoparticles. The RNA nanoparticles with Qβ hp can then be encapsulated into Qβ VLP. We believe this multifunctional VLPs platform has potential to overcome impediments as mentioned earlier and is well suited for nucleic acid-based tools.This dissertation expands our current knowledge on RNA packaging in VLPs and demonstrates proof of concept of combining VLPs with novel RNAi scaffold and cationic polymer as a delivery tool for multiple cargos to mammalian cells.
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