Section of Biological Physics, Department of Physics, Chalmers University of Technology, Göteborg, Sweden and Boreskov Institute of Catalysis, Russian Academy of Sciences, Novosibirsk, Russia.
Phys Rev E. 2017 Oct;96(4-1):042406. doi: 10.1103/PhysRevE.96.042406. Epub 2017 Oct 10.
mRNA delivery into cells forms the basis for one of the new and promising ways to treat various diseases. Among suitable carriers, lipid nanoparticles (LNPs) with a size of about 100 nm are now often employed. Despite high current interest in this area, the understanding of the basic details of LNP-mediated mRNA delivery and function is limited. To clarify the kinetics of mRNA release from LNPs, the author uses three generic models implying (i) exponential, (ii) diffusion-controlled, and (iii) detachment-controlled kinetic regimes, respectively. Despite the distinct differences in these kinetics, the associated transient kinetics of mRNA translation to the corresponding protein and its degradation are shown to be not too sensitive to the details of the mRNA delivery by LNPs (or other nanocarriers). In addition, the author illustrates how this protein may temporarily influence the expression of one gene or a few equivalent genes. The analysis includes positive or negative regulation of the gene transcription via the attachment of the protein without or with positive or negative feedback in the gene expression. Stable, bistable, and oscillatory schemes have been scrutinized in this context.
mRNA 递送入细胞是治疗各种疾病的一种新的、有前途的方法之一。在合适的载体中，现在经常使用大小约为 100nm 的脂质纳米颗粒（LNPs）。尽管目前对此领域的兴趣很高，但对 LNP 介导的 mRNA 递呈和功能的基本细节的理解仍有限。为了阐明 mRNA 从 LNPs 中释放的动力学，作者分别使用了三个通用模型，分别暗示了（i）指数、（ii）扩散控制和（iii）脱离控制的动力学范围。尽管这些动力学有明显的差异，但相关的 mRNA 翻译为相应蛋白质及其降解的瞬时动力学被证明对 LNPs（或其他纳米载体）的 mRNA 递呈的细节不敏感。此外，作者还说明了这种蛋白质如何暂时影响一个或几个等效基因的表达。该分析包括通过蛋白质的附着对基因转录的正或负调节，而无需或具有基因表达中的正或负反馈。在这种情况下，已经仔细研究了稳定、双稳态和振荡方案。
