A careful look at lipid nanoparticle characterization: analysis of benchmark formulations for encapsulation of RNA cargo size gradient.
A careful look at lipid nanoparticle characterization: analysis of benchmark formulations for encapsulation of RNA cargo size gradient.
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仔细观察脂质纳米颗粒表征：分析RNA货物大小梯度封装的基准配方。
DOI：
10.1038/s41598-024-52685-1
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发表时间：
2024-01-29
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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作者：
随着脂质纳米粒（LNP）为基础的SARS-CoV-2 mRNA疫苗的成功，RNA治疗的潜力得到了广泛的关注。LNP是有前途的非病毒递送载体，用于保护和递送脆弱的RNA治疗剂，其是无效的并且易于单独降解。虽然美国食品和药物管理局（FDA）批准的制剂已显示出显著的前景，但基准脂质制剂仍需要优化和改进。此外，这些制剂对于几种不同RNA货物大小的可翻译性尚未在相同条件下进行比较。在本文中，我们分析了“金标准”脂质制剂对各种非特异性RNA货物长度的包裹效率，这些非特异性RNA货物长度代表反义寡核苷酸（阿索）、小干扰RNA（siRNA）、RNA适体和信使RNA（mRNA），长度分别为10个碱基、21个碱基对、96个碱基、996个碱基和1929个碱基。我们将包封效率评价为最终LNP产物中包封的输入RNA的百分比（EE输入%），这与传统的包封效率计算（EE%）显示出差异。当EE%始终> 85%时，所有测试制剂的EE输入%均< 50%。我们还比较了LNP尺寸（Z-平均）和多分散指数（PDI）的制剂。LNP的大小似乎不受货物大小的强烈影响，这是一个违反直觉的发现。LNP的正确表征，与体外或体内行为的考虑并行，将指导设计和优化，以更好地理解和改进未来的RNA治疗。
With the recent success of lipid nanoparticle (LNP) based SARS-CoV-2 mRNA vaccines, the potential for RNA therapeutics has gained widespread attention. LNPs are promising non-viral delivery vectors to protect and deliver delicate RNA therapeutics, which are ineffective and susceptible to degradation alone. While food and drug administration (FDA) approved formulations have shown significant promise, benchmark lipid formulations still require optimization and improvement. In addition, the translatability of these formulations for several different RNA cargo sizes has not been compared under the same conditions. Herein we analyze “gold standard” lipid formulations for encapsulation efficiency of various non-specific RNA cargo lengths representing antisense oligonucleotides (ASO), small interfering RNA (siRNA), RNA aptamers, and messenger RNA (mRNA), with lengths of 10 bases, 21 base pairs, 96 bases, 996 bases, and 1929 bases, respectively. We evaluate encapsulation efficiency as the percentage of input RNA encapsulated in the final LNP product (EEinput%), which shows discrepancy with the traditional calculation of encapsulation efficiency (EE%). EEinput% is shown to be < 50% for all formulations tested, when EE% is consistently > 85%. We also compared formulations for LNP size (Z-average) and polydispersity index (PDI). LNP size does not appear to be strongly influenced by cargo size, which is a counterintuitive finding. Thoughtful characterization of LNPs, in parallel with consideration of in vitro or in vivo behavior, will guide design and optimization for better understanding and improvement of future RNA therapeutics.
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影响因子：
3.7
作者：
Maeki M;Fujishima Y;Sato Y;Yasui T;Kaji N;Ishida A;Tani H;Baba Y;Harashima H;Tokeshi M
通讯作者：
Tokeshi M
影响因子：
17.1
作者：
Kim, Jeonghwan;Jozic, Antony;Lin, Yuxin;Eygeris, Yulia;Bloom, Elissa;Tan, Xiaochen;Acosta, Christopher;MacDonald, Kelvin D.;Welsher, Kevin D.;Sahay, Gaurav
通讯作者：
Sahay, Gaurav
DOI：
10.1016/j.jconrel.2022.02.017
发表时间：
2022-04
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Maeki M;Uno S;Niwa A;Okada Y;Tokeshi M
通讯作者：
Tokeshi M
影响因子：
1.2
作者：
Bailey-Hytholt, Christina M.;Ghosh, Paroma;Bandekar, Amey
通讯作者：
Bandekar, Amey
DOI：
10.1038/mtna.2012.28
发表时间：
2012-08-14
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
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