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Lipids and Lipid Derivatives for RNA Delivery
Chemical Reviews ( IF 51.4 ) Pub Date : 2021-07-19 , DOI: 10.1021/acs.chemrev.1c00244
Yuebao Zhang 1 , Changzhen Sun 1 , Chang Wang 1 , Katarina E Jankovic 1 , Yizhou Dong 1, 2
Affiliation  

RNA-based therapeutics have shown great promise in treating a broad spectrum of diseases through various mechanisms including knockdown of pathological genes, expression of therapeutic proteins, and programmed gene editing. Due to the inherent instability and negative-charges of RNA molecules, RNA-based therapeutics can make the most use of delivery systems to overcome biological barriers and to release the RNA payload into the cytosol. Among different types of delivery systems, lipid-based RNA delivery systems, particularly lipid nanoparticles (LNPs), have been extensively studied due to their unique properties, such as simple chemical synthesis of lipid components, scalable manufacturing processes of LNPs, and wide packaging capability. LNPs represent the most widely used delivery systems for RNA-based therapeutics, as evidenced by the clinical approvals of three LNP-RNA formulations, patisiran, BNT162b2, and mRNA-1273. This review covers recent advances of lipids, lipid derivatives, and lipid-derived macromolecules used in RNA delivery over the past several decades. We focus mainly on their chemical structures, synthetic routes, characterization, formulation methods, and structure–activity relationships. We also briefly describe the current status of representative preclinical studies and clinical trials and highlight future opportunities and challenges.

中文翻译:

用于 RNA 递送的脂质和脂质衍生物

基于 RNA 的疗法在通过各种机制(包括病理基因的敲低、治疗性蛋白质的表达和程序化基因编辑)治疗广泛的疾病方面显示出巨大的希望。由于 RNA 分子固有的不稳定性和负电荷,基于 RNA 的疗法可以充分利用递送系统来克服生物屏障并将 RNA 有效载荷释放到胞质溶胶中。在不同类型的递送系统中,基于脂质的 RNA 递送系统,特别是脂质纳米颗粒 (LNP),由于其独特的特性,例如脂质成分的简单化学合成、LNP 的可扩展制造过程和广泛的包装能力,已被广泛研究. LNP 代表了基于 RNA 的疗法中使用最广泛的递送系统,三种 LNP-RNA 制剂 patisiran、BNT162b2 和 mRNA-1273 的临床批准证明了这一点。这篇综述涵盖了过去几十年来用于 RNA 递送的脂质、脂质衍生物和脂质衍生大分子的最新进展。我们主要关注它们的化学结构、合成路线、表征、配制方法和构效关系。我们还简要描述了具有代表性的临床前研究和临床试验的现状,并强调了未来的机遇和挑战。配制方法和构效关系。我们还简要描述了具有代表性的临床前研究和临床试验的现状,并强调了未来的机遇和挑战。配制方法和构效关系。我们还简要描述了具有代表性的临床前研究和临床试验的现状,并强调了未来的机遇和挑战。
更新日期:2021-07-19
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