Demongeot Jacques, Fougère Cécile
AGEIS & Telecom4Health, Faculty of Medicine, University Grenoble Alpes, 38700 La Tronche, France.
Vaccines (Basel). 2022 Dec 24;11(1):40. doi: 10.3390/vaccines11010040.
The adventure of the mRNA vaccine began thirty years ago in the context of influenza. This consisted in encapsulating the mRNA coding for a viral protein in a lipid particle. We show how the mRNA encoding S protein has been modified for that purpose in the context of the anti-SARS-CoV-2 vaccination.
by using data coming from genetic and epidemiologic databases, we show the theoretical possibility of fragmentation of this mRNA into small RNA sequences capable of inhibiting important bio-syntheses such as the production of beta-globin.
we discuss two aspects related to mRNA vaccine: (i) the plausibility of mRNA fragmentation, and (ii) the role of liposomal nanoparticles (LNPs) used in the vaccine and their impact on mRNA biodistribution.
we insist on the need to develop lipid nanoparticles allowing personalized administration of vaccines and avoiding adverse effects due to mRNA fragmentation and inefficient biodistribution. Hence, we recommend (i) adapting the mRNA of vaccines to the least mutated virus proteins and (ii) personalizing its administration to the categories of chronic patients at risk most likely to suffer from adverse effects.
mRNA疫苗的研发始于三十年前的流感领域。其方法是将编码病毒蛋白的mRNA封装在脂质颗粒中。我们展示了在抗SARS-CoV-2疫苗接种的背景下,编码S蛋白的mRNA是如何为此目的而进行修饰的。
通过使用来自遗传和流行病学数据库的数据,我们展示了这种mRNA断裂成能够抑制重要生物合成(如β-珠蛋白产生)的小RNA序列的理论可能性。
我们讨论了与mRNA疫苗相关的两个方面:(i)mRNA断裂的合理性,以及(ii)疫苗中使用的脂质纳米颗粒(LNP)的作用及其对mRNA生物分布的影响。
我们强调需要开发能够实现疫苗个性化给药的脂质纳米颗粒,避免因mRNA断裂和生物分布效率低下而产生的不良反应。因此,我们建议(i)使疫苗的mRNA适应突变最少的病毒蛋白,以及(ii)针对最有可能出现不良反应的高危慢性病患者类别进行个性化给药。