There are clear differences observed between structural features obtained from these self-assembly simulations in acidic, neutral, and basic environments (Figure ). Self-assembly processes performed under acidic conditions (pH < pKa) mostly generated porous, mesoporous structures similar to what has been observed for other LNP formulations with small-angle X-ray scatter (SAXS) experiments under acidic conditions. Systems that were simulated under neutral conditions (pH ≈ pKa) show the mRNA payload tends to incorporate into the ionizable lipids in either bilayers or tubular structures. Both findings are relevant in regard to elucidating the structural basis for mRNA stabilization and, ultimately, delivery of mRNA in vivo for the following reasons: