modRNA damage in lipid particle manufacturing

Kim Yong-tae, founder and CEO of a Korean nanoparticle production company, attests that mRNA is damaged during its encapsulation in lipid nanoparticles by the shear stress used in the mixing process. To test his hypothesis, he produced lipid nanoparticles under two different flow speeds with one that was used in the manufacturing process and one that is used to create small batches for labs. While encapsulation rates were high for both the mRNA encapsulated in the lipid particles sheared at the manufacturing rate failed to express their protein within cells across multiple modRNA lengths and cell types. Young-Tae theorizes that the shear damage to the modRNA was variably distributed among lots with some vials creating spike protein expression while others did nothing. This may explain the toxic lot observation where only a few lots are found to be responsible for the vast majority of SAEs.

Source: Korea Biomedical Review