“…As discussed above, the immunogenicity has been overcome by chemical modifications; however, the instability of mRNA under physiological conditions requires additional action. Electroporation, 271 gene gun, 272 microinjection, 273 and sonoporation 274 have been investigated for mRNA delivery; however, these are restricted to ex vivo manipulation and ill suited for systemic delivery. Therefore, suitable mRNA carriers should exhibit the following functions: protection from RNase degradation, evasion of direct renal clearance, avoidance of nonspecific interaction, facilitation of mRNA stability, and sufficient mRNA loading and release.…”