为什么mrna离子化LNPs配方如此短暂:原因和出路。

IF 5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Anindita De, Young Tag Ko
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引用次数: 2

摘要

信使核糖核酸(mRNA)和小干扰RNA (siRNA)是可以加热、冷冻、冻干、沉淀或再悬浮而不降解的生物分子。目前,可电离脂质纳米颗粒(LNPs)是一种很有前途的mRNA治疗方法。然而,mrna电离LNPs的长期保质期稳定性是其使用和安全性的开放性问题之一。在酸性pH下,可电离脂质会屏蔽阴离子mRNA。然而,mRNA在储存条件下的稳定性仍然是一个谜。此外,电离LNPs赋形剂在长期储存过程中也会引起不稳定。涵盖领域:本文旨在说明为什么mrna电离LNPs具有如此有限的存储半衰期。本文首次对mRNA-LNPs在制剂辅料中半衰期短、超低温贮藏的原因进行了初步整理。本文还提供了延长mrna电离LNPs长期储存寿命的可能方法。专家意见:mrna离子化LNPs是基因医学的未来。目前配方的局限性可以通过先进的干燥工艺或全新的杂交配方策略来克服,以延长mrna电离LNPs的保质期。这一突破性技术可能为室温下制备热稳定、安全的mrna电离LNPs开辟新的研究方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
CiteScore
11.10
自引率
3.00%
发文量
104
审稿时长
3 months
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.
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