Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang 311121, China.
Chem Soc Rev. 2022 May 23;51(10):3828-3845. doi: 10.1039/d1cs00617g.
The great success achieved by the two highly-effective messenger RNA (mRNA) vaccines during the COVID-19 pandemic highlights the great potential of mRNA technology. Through the evolution of mRNA technology, chemistry has played an important role from mRNA modification to the synthesis of mRNA delivery platforms, which allows various applications of mRNA to be achieved both and . In this tutorial review, we provide a summary and discussion on the significant progress of emerging mRNA technologies, as well as the underlying chemical designs and principles. Various nanoparticle (NP)-based delivery strategies including protein-mRNA complex, lipid-based carriers, polymer-based carriers, and hybrid carriers for the efficient delivery of mRNA molecules are presented. Furthermore, typical mRNA delivery platforms for various biomedical applications (, functional protein expression, vaccines, cancer immunotherapy, and genome editing) are highlighted. Finally, our insights into the challenges and future development towards clinical translation of these mRNA technologies are provided.
在 COVID-19 大流行期间,两种高效的信使 RNA(mRNA)疫苗取得了巨大成功,突显了 mRNA 技术的巨大潜力。通过 mRNA 技术的发展,化学在 mRNA 修饰到 mRNA 递药平台的合成过程中发挥了重要作用,这使得 mRNA 的各种应用得以在体内和体外实现。在本综述教程中,我们对新兴的 mRNA 技术的重要进展进行了总结和讨论,并介绍了底层的化学设计和原理。我们提出了各种基于纳米颗粒(NP)的递药策略,包括用于高效递送 mRNA 分子的蛋白-mRNA 复合物、基于脂质的载体、基于聚合物的载体和杂合载体。此外,还重点介绍了用于各种生物医学应用(如功能性蛋白表达、疫苗、癌症免疫疗法和基因组编辑)的典型 mRNA 递药平台。最后,我们对这些 mRNA 技术向临床转化所面临的挑战和未来发展方向提出了看法。