Laboratory of Gene Therapy, Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, B-9820 Merelbeke, Belgium.
SINTEF Industry, Dept. of Biotechnology and Nanomedicine, Research Group Mass Spectrometry, Sem Sælands v. 2A, N-7034 Trondheim, Norway.
Adv Drug Deliv Rev. 2022 May;184:114236. doi: 10.1016/j.addr.2022.114236. Epub 2022 Mar 26.
The success of the messenger RNA-based COVID-19 vaccines of Moderna and Pfizer/BioNTech marks the beginning of a new chapter in modern medicine. However, the rapid rise of mRNA therapeutics has resulted in a regulatory framework that is somewhat lagging. The current guidelines either do not apply, do not mention RNA therapeutics, or do not have widely accepted definitions. This review describes the guidelines for preclinical biodistribution studies of mRNA/siRNA therapeutics and highlights the relevant differences for mRNA vaccines. We also discuss the role of in vivo RNA imaging techniques and other assays to fulfill and/or complement the regulatory requirements. Specifically, quantitative whole-body autoradiography, microautoradiography, mass spectrometry-based assays, hybridization techniques (FISH, bDNA), PCR-based methods, in vivo fluorescence imaging, and in vivo bioluminescence imaging, are discussed. We conclude that this new and rapidly evolving class of medicines demands a multi-layered approach to fully understand its biodistribution and in vivo characteristics.
信使 RNA 新冠疫苗（由 Moderna 和辉瑞/生物科技研发）的成功标志着现代医学新篇章的开始。然而，mRNA 疗法的快速崛起导致监管框架有些滞后。目前的指南要么不适用，要么没有提到 RNA 疗法，要么没有广泛接受的定义。这篇综述描述了 mRNA/siRNA 疗法的临床前生物分布研究指南，并强调了 mRNA 疫苗的相关差异。我们还讨论了体内 RNA 成像技术和其他检测方法的作用，以满足和/或补充监管要求。具体而言，定量全身放射自显影、显微放射自显影、基于质谱的检测方法、杂交技术（FISH、bDNA）、基于 PCR 的方法、体内荧光成像和体内生物发光成像都进行了讨论。我们的结论是，这种新型的、快速发展的药物类别需要采用多层次的方法来全面了解其生物分布和体内特征。
