||Hao-Han Pang |
|Author's Email Address
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||Institute of Medical Science and Technology|
|Type of Document
||Using Multifunctional Qβ Virus-Like Particles for RNAi and Reducing Temozolomide Resistance in Brain Tumor|
|Date of Defense
Brain tumour is one of the most lethal cancers due to difficulties of delivering therapeutic agents across blood-brain barrier (BBB) and serious side effect. Here, we describe a virus-like particles (VLPs) platform as multifunctional nanocarriers to deliver RNA molecules and fluorescence proteins for RNA interference and imaging tracking.
We have designed an RNA scaffold and co-expressed with Qβ coat protein and green fluorescent protein (GFP) or mCherry protein simultaneously through a two-plasmid system. Coat proteins and cargos will be produced and self assembled in E. coli. The TAT and ApoE peptide, were then incorporated to the exterior surface of VLPs via a linker (sulfo-SMCC) to enhance cell uptake and promote BBB penetration.
The functional VLPs have been assessed by cell examination. VLPs do not show cytotoxicity and can be internalized insides cells. VLPs containing RNA molecules and GFP modulate gene expression and serve as fluorescent trackers within U87 cells. VLPs containing RNAi scaffold for c-MET silencing and GFP (c-MET@t-gVLPs) successfully down regulated the c-MET protein expression level of U87 cell. c-MET@t-gVLPs treated cells also showed lower Temozolomide (TMZ) drug resistance and limited cell migration.
ApoE conjugated VLPs have the ability to cross the BBB in vivo. Current findings showed that our VLPs could be a good RNAi delivery plateform for gene down-regulation therapy.
We believe this multifunctional VLP platform has potential to overcome impediments as mentioned earlier and well suited for RNAi-based therapeutic tools for brain tumour therapy.
||Kuo-Chen Wei - chair|
Chiao-Long Hsiao - co-chair
Hung-Wei Yang - advisor
Indicate in-campus at 3 year and off-campus access at 5 year.|
|Date of Submission