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This study shows that LNP generated by automatic Qualcomm platform shows enhanced mRNA delivery efficiency in vitro and in vivo, which provides valuable insights for enhancing functional delivery of mRNA and helps to accelerate the development of future mRNA therapy or vaccine.
Writing | Xiao Jing
Editor | Wang Duoyu
Typesetting | water writing
Due to the prevalence of coronavirus pneumonia-19 and the appearance of mRNA vaccine, mRNA technology as a new treatment method has attracted wide attention. The vaccine of mRNA has many advantages, and it can be instantly expressed as protein in cytoplasm. MRNA can also be used in tumor immunotherapy, protein substitution, gene editing and cell therapy in vitro. However, the disadvantages of mRNA, such as immunogenicity, sensitivity to RNA and short half-life, seriously limit the application of mRNA. Therefore, it is of great significance to construct new vectors to optimize the delivery strategy of mRNA, thus reducing the immunogenicity of mRNA and increasing the delivery stability. Recently, AstraZeneca Cui Lili and others published a journal entitled "Mechanical research of automated lipid nanoparticles reveals key drug characteristics related to enhancing small molecular magnetic resonance". Functional transport of sodium in vivo and in vitro. The research team developed an automated Qualcomm platform for screening ionizable lipid nanoparticles (LNP) to enhance intracellular functional delivery of mRNA, and revealed the mechanism of enhancing mRNA delivery to cytoplasm. Compared with LNP prepared by traditional technology, the mRNA delivery efficiency of LNP produced by automation technology in vivo is improved by 4.5 times. [Image upload failed ... (Picture -606c98- 1648805499632)]
In this study, the ionized liposome DLin-MC3-DMA (MC3) was used as the reference lipid, and the mRNA LNP was prepared by automatic preparation technology and standard microfluidic technology. Its morphology and structure were characterized by dynamic light scattering (DLS), frozen electron microscope, SANS and SAXS. It was found that the hydrodynamic size and polydispersity index (PDI) of automated mRNA LNP were larger than those of standard mRNA LNP. The shell volume of automatic mRNA LNP is 1.6 times that of standard mRNA LNP, and its surface is more hydrophobic. [Image upload failed ... (Picture-694122-1648805499632)]
PH-sensitive behavior is very important for LNP endosome escape. By studying protonation and hemolysis in acid buffer, the research team studied the pH sensitive behavior of two mRNA LNP. Among them, the hemolysis rate induced by automated mRNA LNP is much faster than that of standard mRNA LNP, so automated mRNA LNP has the ability to escape from the endosome and enter the cytoplasm faster than standard mRNA LNP. Next, the research team studied the translation efficiency of two LNP-delivered mRNA in vivo by comparing the bioluminescence intensity of luciferase protein in mice. The experimental results show that the luminescence intensity of automatic mRNA LNP group at 6 hours and 24 hours is significantly higher than that of standard mRNA LNP group, which indicates that automatic LNP can enhance the functional delivery of mRNA. [Image upload failed ... (Picture-19F324-1648805499632)]
Finally, the research team explored the potential mechanism of automatic LNP enhancing mRNA function transmission in vivo. LNP particles with large size can accommodate more mRNA, have more hydrophobic surfaces, are more hemolytic, bind larger protein crowns, and tend to accumulate more in large cytoplasmic bodies, so it is more conducive to transporting mRNA to cytoplasm in quantity. Generally speaking, this study shows that LNP generated by using the automated Qualcomm platform shows enhanced mRNA delivery efficiency in vitro and in vivo, which provides valuable insights for enhancing functional delivery of mRNA and helps to accelerate the development of future mRNA therapy or vaccine. Paper connection:/doi/10.1002/smll.202105832