{"title":"rna -脂质纳米颗粒治疗分析分离技术的挑战与进展。","authors":"Brady W Drennan, Kevin A Schug","doi":"10.1007/s00216-025-06096-4","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Challenges and advances in analytical separation techniques for RNA-lipid nanoparticle therapeutics.\",\"authors\":\"Brady W Drennan, Kevin A Schug\",\"doi\":\"10.1007/s00216-025-06096-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":462,\"journal\":{\"name\":\"Analytical and Bioanalytical Chemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2025-09-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Analytical and Bioanalytical Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1007/s00216-025-06096-4\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Analytical and Bioanalytical Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s00216-025-06096-4","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Challenges and advances in analytical separation techniques for RNA-lipid nanoparticle therapeutics.
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.
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.