Optimization of storage conditions for lipid nanoparticle-formulated self-replicating RNA vaccines.
Optimization of storage conditions for lipid nanoparticle-formulated self-replicating RNA vaccines.
复制标题
脂质纳米颗粒形成的自我复制RNA疫苗的储存条件的优化。
DOI：
10.1016/j.jconrel.2022.11.022
复制
发表时间：
2023-01
影响因子：
10.8
通讯作者：
Irvine, Darrell J.
中科院分区：
文献类型：
--
作者：
Kim, Byungji;Hosn, Ryan R.;Remba, Tanaka;Yun, Dongsoo;Li, Na;Abraham, Wuhbet;Melo, Mariane B.;Cortes, Manuel;Li, Bridget;Zhang, Yuebao;Dong, Yizhou;Irvine, Darrell J.
最近多种基于mRNA的SARS-CoV-2疫苗的临床成功已经证明了脂质纳米颗粒（LNP）中配制的RNA在人类中的潜力，并且基于碱基修饰的RNA、序列优化的RNA和在LNP中配制的自我复制的RNA的产品都处于临床开发的不同阶段。然而，关于控制LNP-RNA制剂的制造和使用的关键参数仍有许多有待了解。迄今为止，在文献中受到有限关注的一个重要问题是确定保持制剂长期活性的LNP-RNA的最佳储存条件。在这里，我们分析了甲病毒衍生的自我复制RNA（repRNA）加载的LNP编码HIV疫苗抗原的物理结构，体内表达特征和功能活性，这些LNP在不同的温度，缓冲液和存在或不存在冷冻保护剂的情况下储存。我们发现，对于具有与临床使用的LNP相似的组成的脂质纳米颗粒，在-20 °C下储存在含有10%（w/v）蔗糖的无RNA酶PBS中能够在储存30天后将疫苗稳定性和体内效力维持在与新鲜制备的疫苗相当的水平。负载有repRNA的LNP也可以冻干而保留生物活性。
The recent clinical success of multiple mRNA-based SARS-CoV-2 vaccines has proven the potential of RNA formulated in lipid nanoparticles (LNPs) in humans, and products based on base-modified RNA, sequence-optimized RNA, and self-replicating RNAs formulated in LNPs are all in various stages of clinical development. However, much remains to be learned about critical parameters governing the manufacturing and use of LNP-RNA formulations. One important issue that has received limited attention in the literature to date is the identification of optimal storage conditions for LNP-RNA that preserve long-term activity of the formulations. Here, we analyzed the physical structure, in vivo expression characteristics, and functional activity of alphavirus-derived self-replicating RNA (repRNA)-loaded LNPs encoding HIV vaccine antigens following storage in varying temperatures, buffers, and in the presence or absence of cryoprotectants. We found that for lipid nanoparticles with compositions similar to clinically-used LNPs, storage in RNAse-free PBS containing 10% (w/v) sucrose at −20 °C was able to maintain vaccine stability and in vivo potency at a level equivalent to freshly prepared vaccines following 30 days of storage. LNPs loaded with repRNA could also be lyophilized with retention of bioactivity.
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影响因子：
5.5
作者：
Hatziantoniou S;Maltezou HC;Tsakris A;Poland GA;Anastassopoulou C
通讯作者：
Anastassopoulou C
DOI：
10.1038/s41578-021-00358-0
发表时间：
2021
期刊：
Nature reviews. Materials
影响因子：
--
作者：
Hou X;Zaks T;Langer R;Dong Y
通讯作者：
Dong Y
影响因子：
5.9
作者：
Carrasco MJ;Alishetty S;Alameh MG;Said H;Wright L;Paige M;Soliman O;Weissman D;Cleveland TE 4th;Grishaev A;Buschmann MD
通讯作者：
Buschmann MD
影响因子：
64.8
作者：
Gebre MS;Rauch S;Roth N;Yu J;Chandrashekar A;Mercado NB;He X;Liu J;McMahan K;Martinot A;Martinez DR;Giffin V;Hope D;Patel S;Sellers D;Sanborn O;Barrett J;Liu X;Cole AC;Pessaint L;Valentin D;Flinchbaugh Z;Yalley-Ogunro J;Muench J;Brown R;Cook A;Teow E;Andersen H;Lewis MG;Boon ACM;Baric RS;Mueller SO;Petsch B;Barouch DH
通讯作者：
Barouch DH
影响因子：
3.4
作者：
Brader ML;Williams SJ;Banks JM;Hui WH;Zhou ZH;Jin L
通讯作者：
Jin L