Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/209002
Title: TRANSLATION ENHANCEMENT OF IN-VITRO-TRANSCRIBED MESSENGER RNA BY INFLUENZA A VIRUS DERIVED NON-STRUCTURAL PROTEIN 1
Authors: LIU YI
Keywords: IVT mRNA, transfection, immune evasion, NS1, interferon, mRNA therapeutics
Issue Date: 8-Aug-2019
Citation: LIU YI (2019-08-08). TRANSLATION ENHANCEMENT OF IN-VITRO-TRANSCRIBED MESSENGER RNA BY INFLUENZA A VIRUS DERIVED NON-STRUCTURAL PROTEIN 1. ScholarBank@NUS Repository.
Abstract: In this thesis, we show our exploration of applying influenza A virus derived non-structural protein 1 (NS1) to modulate immunogenicity and translation capacity of in vitro-transcribed (IVT) mRNA. Co-transfection of mRNA encoding NS1 and reporter gene mRNA enhanced reporter gene expression by over 10 times. NS1’s inhibition of interferon regulatory factor 3 (IRF3), protein kinase RNA-activated (PKR), and most importantly cleavage and polyadenylation factor 30kDa (CPSF30) was found to be contributing mechanism. One single intramuscular co-injection of NS1 mRNA and reporter gene mRNA was shown to mediate great enhancement of reporter gene expression and prolong the kinetics of expression by up to 7 days. In a protein therapy model, co-injection of NS1 mRNA and erythropoietin mRNA significantly increased hematocrit of treated mice. In a vaccination model, co-injection of NS1 mRNA, interferon mRNA and antigen mRNA not only promised sustained antigen expression, but also induced stronger antibody response against antigen.
URI: https://scholarbank.nus.edu.sg/handle/10635/209002
Appears in Collections:Ph.D Theses (Open)

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