(R)-C12-200, an ionizable cationic lipid (pKa = 7.25) and isomer of C12-200, is utilized in forming lipid nanoparticles (LNPs) for delivering mRNA in vivo. When administered intravenously, LNPs containing (R)-C12-200 with mRNA encoding Cre recombinase result in a smaller increase in the percentage of tdTomato+ hepatocytes, endothelial cells, and Kupffer cells in the liver of Ai14 mice compared to LNPs with (S)-C12-200. Additionally, LNPs with (R)-C12-200 carrying mRNA for purine nucleoside phosphorylase (PNP), an E. coli enzyme that transforms fludarabine phosphate into the cytotoxic agent 2-fluoroadenine, prompt intratumoral PNP expression and diminish tumor volume in a FaDu head and neck squamous cell carcinoma (HNSCC) mouse xenograft model when fludarabine phosphate is co-administered.

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