Abstract: Lipid nanoparticle (LNP) encapsulating self-amplifying mRNA, compositions, and methods of using the novel nucleic acid constructs and compositions are disclosed. LNP constructs include novel ionizable lipid. Novel sa-mRNA constructs encode a modified SARS-CoV-2 spike protein, wherein the polynucleotide has been truncated to not include nucleotides encoding a SARS-CoV-2 transmembrane domain and short cytosolic domain amino acids and immunomodulators. Sa-mRNAs are useful in for use as a therapeutic, diagnostic and/or prophylactic agent to mammalian cells or organs.

Abstract: Novel ionizable lipids, compositions, and methods of using the novel ionizable lipids and compositions are disclosed. Lipid nanoparticle compositions include a novel ionizable lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Lipid nanoparticle compositions further including biologically active agents such as mRNA or DNA are useful in the delivery of biologically active agents to mammalian cells or organs.