{"title":"为什么mrna离子化LNPs配方如此短暂:原因和出路。","authors":"Anindita De, Young Tag Ko","doi":"10.1080/17425247.2023.2162876","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Messenger ribonucleic acid (mRNA) and small interfering RNA (siRNA) are biological molecules that can be heated, frozen, lyophilized, precipitated, or re-suspended without degradation. Currently, ionizable lipid nanoparticles (LNPs) are a promising approach for mRNA therapy. However, the long-term shelf-life stability of mRNA-ionizable LNPs is one of the open questions about their use and safety. At an acidic pH, ionizable lipids shield anionic mRNA. However, the stability of mRNA under storage conditions remains a mystery. Moreover, ionizable LNPs excipients also cause instability during long-term storage.</p><p><strong>Area covered: </strong>This paper aims to illustrate why mRNA-ionizable LNPs have such a limited storage half-life. For the first time, we compile the tentative reasons for the short half-life and ultra-cold storage of mRNA-LNPs in the context of formulation excipients. The article also provided possible ways of prolonging the lifespan of mRNA-ionizable LNPs during long storage.</p><p><strong>Expert opinion: </strong>mRNA-ionizable LNPs are the future of genetic medicine. Current limitations of the formulation can be overcome by an advanced drying process or a whole new hybrid formulation strategy to extend the shelf life of mRNA-ionizable LNPs. A breakthrough technology may open up new research directions for producing thermostable and safe mRNA-ionizable LNPs at room temperature.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":"20 2","pages":"175-187"},"PeriodicalIF":5.0000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Why mRNA-ionizable LNPs formulations are so short-lived: causes and way-out.\",\"authors\":\"Anindita De, Young Tag Ko\",\"doi\":\"10.1080/17425247.2023.2162876\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Messenger ribonucleic acid (mRNA) and small interfering RNA (siRNA) are biological molecules that can be heated, frozen, lyophilized, precipitated, or re-suspended without degradation. Currently, ionizable lipid nanoparticles (LNPs) are a promising approach for mRNA therapy. However, the long-term shelf-life stability of mRNA-ionizable LNPs is one of the open questions about their use and safety. At an acidic pH, ionizable lipids shield anionic mRNA. However, the stability of mRNA under storage conditions remains a mystery. Moreover, ionizable LNPs excipients also cause instability during long-term storage.</p><p><strong>Area covered: </strong>This paper aims to illustrate why mRNA-ionizable LNPs have such a limited storage half-life. For the first time, we compile the tentative reasons for the short half-life and ultra-cold storage of mRNA-LNPs in the context of formulation excipients. The article also provided possible ways of prolonging the lifespan of mRNA-ionizable LNPs during long storage.</p><p><strong>Expert opinion: </strong>mRNA-ionizable LNPs are the future of genetic medicine. Current limitations of the formulation can be overcome by an advanced drying process or a whole new hybrid formulation strategy to extend the shelf life of mRNA-ionizable LNPs. A breakthrough technology may open up new research directions for producing thermostable and safe mRNA-ionizable LNPs at room temperature.</p>\",\"PeriodicalId\":12229,\"journal\":{\"name\":\"Expert Opinion on Drug Delivery\",\"volume\":\"20 2\",\"pages\":\"175-187\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2023-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Opinion on Drug Delivery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17425247.2023.2162876\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Drug Delivery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17425247.2023.2162876","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Why mRNA-ionizable LNPs formulations are so short-lived: causes and way-out.
Introduction: Messenger ribonucleic acid (mRNA) and small interfering RNA (siRNA) are biological molecules that can be heated, frozen, lyophilized, precipitated, or re-suspended without degradation. Currently, ionizable lipid nanoparticles (LNPs) are a promising approach for mRNA therapy. However, the long-term shelf-life stability of mRNA-ionizable LNPs is one of the open questions about their use and safety. At an acidic pH, ionizable lipids shield anionic mRNA. However, the stability of mRNA under storage conditions remains a mystery. Moreover, ionizable LNPs excipients also cause instability during long-term storage.
Area covered: This paper aims to illustrate why mRNA-ionizable LNPs have such a limited storage half-life. For the first time, we compile the tentative reasons for the short half-life and ultra-cold storage of mRNA-LNPs in the context of formulation excipients. The article also provided possible ways of prolonging the lifespan of mRNA-ionizable LNPs during long storage.
Expert opinion: mRNA-ionizable LNPs are the future of genetic medicine. Current limitations of the formulation can be overcome by an advanced drying process or a whole new hybrid formulation strategy to extend the shelf life of mRNA-ionizable LNPs. A breakthrough technology may open up new research directions for producing thermostable and safe mRNA-ionizable LNPs at room temperature.
期刊介绍:
Expert Opinion on Drug Delivery (ISSN 1742-5247 [print], 1744-7593 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles covering all aspects of drug delivery research, from initial concept to potential therapeutic application and final relevance in clinical use. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.