Challenges and advances in analytical separation techniques for RNA-lipid nanoparticle therapeutics.

IF 3.8 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS
Brady W Drennan, Kevin A Schug
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引用次数: 0

Abstract

Gene therapies are rapidly advancing as drug modalities, serving as a means to treat previously undruggable pathways. The use of small interfering ribonucleic acid (siRNA), messenger RNA (mRNA), and guide RNA (gRNA) in clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing, combined with lipid nanoparticles (LNPs), has demonstrated effective drug delivery. These complex delivery systems often require multiple analytical methodologies to achieve comprehensive characterization, some of which remain underdeveloped or inadequately adapted for RNA-LNP formulations. Commonly used batch-based methods, such as dynamic light scattering (DLS) or the modified RiboGreen assay, are frequently hindered by sample heterogeneity, a limitation that can be addressed through analytical separations. This review discusses the challenges limiting analytical separations for RNA-LNP therapeutics and highlights recent advances in separation science for reliable characterization and quality control. We focus on techniques for RNA, LNPs, and the RNA-LNP complex, emphasizing chromatographic, electrophoretic, and field-based separation techniques.

rna -脂质纳米颗粒治疗分析分离技术的挑战与进展。
基因疗法作为一种药物形式正在迅速发展,作为治疗以前无法治疗的途径的一种手段。小干扰核糖核酸(siRNA)、信使RNA (mRNA)和引导RNA (gRNA)在聚集规律间隔短回文重复序列(CRISPR)为基础的基因编辑中,结合脂质纳米颗粒(LNPs),已被证明是有效的药物递送。这些复杂的给药系统通常需要多种分析方法来实现全面的表征,其中一些方法仍然不发达或不适合RNA-LNP配方。常用的基于批处理的方法,如动态光散射(DLS)或改进的RiboGreen测定法,经常受到样品异质性的阻碍,这一限制可以通过分析分离来解决。这篇综述讨论了限制RNA-LNP治疗学分析分离的挑战,并强调了分离科学在可靠表征和质量控制方面的最新进展。我们专注于RNA、lnp和RNA- lnp复合物的技术,强调色谱、电泳和基于场的分离技术。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.00
自引率
4.70%
发文量
638
审稿时长
2.1 months
期刊介绍: Analytical and Bioanalytical Chemistry’s mission is the rapid publication of excellent and high-impact research articles on fundamental and applied topics of analytical and bioanalytical measurement science. Its scope is broad, and ranges from novel measurement platforms and their characterization to multidisciplinary approaches that effectively address important scientific problems. The Editors encourage submissions presenting innovative analytical research in concept, instrumentation, methods, and/or applications, including: mass spectrometry, spectroscopy, and electroanalysis; advanced separations; analytical strategies in “-omics” and imaging, bioanalysis, and sampling; miniaturized devices, medical diagnostics, sensors; analytical characterization of nano- and biomaterials; chemometrics and advanced data analysis.
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