Lipid Nanoparticles for Organ-Specific mRNA Therapeutic Delivery.

This article belongs to the Special Issue mRNA Therapeutics: A Themed Issue in Honor of Professor Katalin Karikó. Advances in the using in vitro transcribed (IVT) modRNA in the past two decades, especially the tremendous recent success of mRNA vaccines against SARS-CoV-2, have brought increased attention to IVT mRNA technology. Despite its well-known use in infectious disease vaccines, IVT modRNA technology is being investigated mainly in cancer immunotherapy and protein replacement therapy, with ongoing clinical trials in both areas. One of the main barriers to progressing mRNA therapeutics to the clinic is determining how to deliver mRNA to target cells and protect it from degradation. Over the years, many different vehicles have been developed to tackle this issue. Desirable vehicles must be safe, stable and preferably organ specific for successful mRNA delivery to clinically relevant cells and tissues. In this review we discuss various mRNA delivery platforms, with particular focus on attempts to create organ-specific vehicles for therapeutic mRNA delivery.

本文属于《mRNA疗法：纪念卡塔林·卡里科教授特刊》。 过去二十年来，体外转录（IVT）修饰mRNA的应用取得了进展，特别是近期mRNA新冠疫苗取得的巨大成功，使IVT mRNA技术受到了更多关注。尽管其在传染病疫苗中的应用已广为人知，但IVT修饰mRNA技术主要在癌症免疫疗法和蛋白质替代疗法中进行研究，这两个领域都有正在进行的临床试验。将mRNA疗法推向临床的主要障碍之一是确定如何将mRNA递送至靶细胞并保护其免受降解。多年来，已经开发了许多不同的载体来解决这一问题。理想的载体必须安全、稳定，最好具有器官特异性，以便将mRNA成功递送至临床相关的细胞和组织。在这篇综述中，我们讨论了各种mRNA递送平台，特别关注了创建用于治疗性mRNA递送的器官特异性载体的尝试。