研究生如此读新闻-第10期 mRNA 疫苗

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2022年5月30日新闻：Sanofi 和 EUROAPI 公司合作，开发脂质纳米粒mRNA 疫苗项目.

https://www.biopharma-reporter.com/Article/2022/05/30/euroapi-supports-sanofi-s-mrna-vaccine-projects-with-lipid-nanoparticle-development


Lipid nanoparticles play a crucial role in their ability to encapsulate, protect and transport mRNA to the cells.

脂质纳米颗粒在包裹、保护和运输mRNA到细胞中起着至关重要的作用。

我找到了相关的文献支持：

https://www.nature.com/articles/s41578-021-00358-0

Lipid nanoparticle–mRNA formulations as COVID-19 vaccines.

Messenger RNA (mRNA) is a transient intermediator between genes and proteins.

Gene expression

信使RNA (Messenger RNA, mRNA)是基因和蛋白质之间的一种短暂的中介物。

To achieve therapeutic effects, mRNA molecules have to reach specific target cells and produce sufficient proteins of interest. However, targeted delivery and endosomal escape remain challenging for mRNA delivery systems, highlighting the need for safe and effective mRNA delivery materials.

为了达到治疗效果，mRNA分子必须到达特定的靶细胞并产生足够的特异的蛋白质。然而，靶向给药和胞内逃逸对mRNA给药系统仍然具有挑战性，这突出了对安全有效的mRNA给药材料的需求。

Timeline of some key milestones for mRNA and lipid nanoparticle development

Chemical structures of lipids and lipid derivatives used for mRNA delivery

Lipids are amphiphilic molecules that contain three domains: a polar head group, a hydrophobic tail region and a linker between the two domains. Cationic lipids, ionizable lipids and other types of lipid have been explored for mRNA delivery

脂类是两亲性分子，包含三个结构域:极性头部，疏水尾区和两个结构域之间的连接片段。阳离子脂质、可电离脂质和其他类型的脂质已被探索用于mRNA的传递。

To function invivo, lipid nanoparticle–mRNA formulations need to overcome multiple extracellular and intracellular barriers. First, mRNA needs to be protected from nuclease degradation in physiological fluids. Second, the formulation should evade the interception by the MPS and clearance by renal glomerular filtration post systemic administration. Third, lipid nanoparticle–mRNA systems need to reach target tissues, followed by internalization by target cells. Finally, mRNA molecules must escape endosomes to reach the cytoplasm, where translation occurs.

为了在体内有效，脂质纳米颗粒-mRNA 制剂需要克服细胞内和细胞外的多重障碍。首先，mRNA 需要被保护免遭体液中核酸酶降解；其次，该制剂应避开单核吞噬细胞系统的截留和全身给药后肾小球滤过的清除；再次，脂质纳米颗粒-mRNA 制剂需要先到达靶组织，然后被靶细胞吞入；最后，mRNA必须逃离内含体到达转录发生的细胞质。

Delivery barriers and administration routes for lipid nanoparticle–mRNA formulations.

Representative clinical trials of lipid nanoparticle–mRNA vaccines against infections and cancer

Representative clinical trials of lipid nanoparticle–mRNA vaccines against infections and cancer