Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.
University of Chinese Academy of Sciences, Beijing, 100490, P. R. China.
Chembiochem. 2023 May 2;24(9):e202200801. doi: 10.1002/cbic.202200801. Epub 2023 Mar 30.
Messenger RNA (mRNA) is being used as part of an emerging class of biotherapeutics with great promise for preventing and treating a wide range of diseases, as well as encoding programmable nucleases for genome editing. However, mRNA's low stability and immunogenicity, as well as the impermeability of the cell membrane to mRNA greatly limit mRNA's potential for therapeutic use. Lipid nanoparticles (LNPs) are currently one of the most extensively studied nanocarriers for mRNA delivery and have recently been clinically approved for developing mRNA-based vaccines to prevent COVID-19. In this review, we summarize the latest advances in designing ionizable lipids and formulating LNPs for intracellular and tissue-targeted mRNA delivery. Furthermore, we discuss the progress of intracellular mRNA delivery for spatiotemporally controlled CRISPR/Cas9 genome editing by using LNPs. Finally, we provide a perspective on the future of LNP-based mRNA delivery for CRISPR/Cas9 genome editing and the treatment of genetic disorders.
信使 RNA（mRNA）正被用作一类新兴生物疗法的一部分，具有预防和治疗广泛疾病的巨大潜力，同时也可以编码可编程核酸酶用于基因组编辑。然而，mRNA 的低稳定性和免疫原性，以及细胞膜对 mRNA 的不渗透性，极大地限制了其在治疗中的应用。脂质纳米颗粒（LNPs）是目前研究最广泛的 mRNA 递送纳米载体之一，最近已被临床批准用于开发基于 mRNA 的疫苗以预防 COVID-19。在这篇综述中，我们总结了设计可离子化脂质和配制 LNPs 以实现细胞内和组织靶向 mRNA 递送的最新进展。此外，我们还讨论了利用 LNPs 进行时空可控 CRISPR/Cas9 基因组编辑的细胞内 mRNA 递送的进展。最后，我们对基于 LNP 的 mRNA 递送用于 CRISPR/Cas9 基因组编辑和遗传疾病治疗的未来进行了展望。
