Abstract: In the various aspects and embodiments, this disclosure provides messenger RNA (mRNA) constructs for therapeutic delivery, as well as methods for making such mRNA constructs and pharmaceutical compositions comprising the same (including mRNA vaccine compositions). In still other aspects, the invention provides methods for treating patients by expression of therapeutic proteins, including for preventing or reducing probability of infection by, or illness involving, a virus. Exemplary viruses include coronaviruses (such as SARS-CoV-2 and variants therefore) and influenza viruses, among others.