Global warming and the threat of the emergence or reemergence of mosquito-borne Flavivirus infections such as West Nile/Kunjin virus (KUNV), Murray Valley encephalitis virus (MVEV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) necessitate innovative prevention and therapeutic strategies. Our extensive research on Flavivirus infection and vaccination has been re-directed onto mRNA technology to generate new vaccines, therapeutic antibodies and diagnostics to counteract these pathogens. Our approach with Virus-Like Particles (VLPs) protein vaccines (Ref 1,2) has guided the design of mRNA molecules designed to express non-infectious VLPs aimed at inducing strong immune response in-vivo. Testing in animal models will permit subsequent antibody production. VLP protein designs that we previously validated in an adenovirus expression system, known for producing high-yield VLPs, were re-programmed into plasmid templates that were used for T7-RNA-pol in-vitro transcription (IVT) of pseudouridine-modified mRNAs incorporating a 5′ Cleancap, with optimized 5′ and 3′ UTR, and a poly(A) tail. Experiments transfecting purified IVT mRNA into human cell lines confirmed high levels of viral envelope protein for MVEV and KUNV using immunofluorescence assays (IFA), Western Blot (WB), and Enzyme-Linked Immunosorbent Assays (ELISAs). However, the expression levels achieved for ZIKV and JEV were more modest, especially compared to those obtained via the adenovirus system. Currently, the mRNA formulation are being prepared for animal immunizations and assessment of neutralizing antibody production. Ongoing research focuses on further optimizing mRNA constructs and delivery methods to enhance protein expression to maximize immunogenicity. This study underscores the promise of mRNA-powered vaccines, especially for the production of new monoclonal antibodies, to prevent and treat against important Flavivirus infections in our region.