Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery.
Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery.
复制标题
使用多种技术方法制备选择性器官靶向 (SORT) 脂质纳米粒子 (LNP)，用于组织特异性 mRNA 递送。
DOI：
10.1038/s41596-022-00755-x
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发表时间：
2023-01
期刊：
影响因子：
14.8
通讯作者：
Siegwart, Daniel J.
中科院分区：
文献类型：
--
作者：
Wang, Xu;Liu, Shuai;Sun, Yehui;Yu, Xueliang;Lee, Sang M.;Cheng, Qiang;Wei, Tuo;Gong, Junyu;Robinson, Joshua;Zhang, Di;Lian, Xizhen;Basak, Pratima;Siegwart, Daniel J.
A new methodology termed selective organ targeting (SORT) was recently developed that enables controllable delivery of nucleic acids to target tissues. SORT lipid nanoparticles (LNPs) involve the inclusion of SORT molecules that accurately tune delivery to the liver, lungs and spleen of mice after intravenous administration. Nanoparticles can be engineered to target specific cells and organs in the body by passive, active and endogenous targeting mechanisms that require distinct design criteria. SORT LNPs are modular and can be prepared using scalable, synthetic chemistry and established engineering formulation methods. This protocol provides detailed procedures, including the synthesis of a representative ionizable cationic lipid, preparation of multiple classes of SORT LNPs by pipette, vortex and microfluidic mixing methods, physical characterization, and in vitro/in vivo mRNA delivery evaluation. Depending on the scale of the experiments, the synthesis of the ionizable lipid requires 4–6 d; LNPs can be formulated within several hours; LNP characterization can be completed in 2–4 h; and in vitro/in vivo evaluation studies require 1–14 d, depending on the design and application. Our strategy offers a versatile and practical method for rationally designing nanoparticles that accurately target specific organs. The SORT LNPs generated as described in this protocol can therefore be applied to multiple classes of LNP systems for therapeutic nucleic acid delivery and facilitate the development of protein replacement and genetic medicines in target tissues. This protocol does not require specific expertise, is modular to various lipids within defined physicochemical classes, and should be accomplishable by researchers from various backgrounds.
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影响因子：
32.4
作者：
Alameh MG;Tombácz I;Bettini E;Lederer K;Sittplangkoon C;Wilmore JR;Gaudette BT;Soliman OY;Pine M;Hicks P;Manzoni TB;Knox JJ;Johnson JL;Laczkó D;Muramatsu H;Davis B;Meng W;Rosenfeld AM;Strohmeier S;Lin PJC;Mui BL;Tam YK;Karikó K;Jacquet A;Krammer F;Bates P;Cancro MP;Weissman D;Luning Prak ET;Allman D;Locci M;Pardi N
通讯作者：
Pardi N
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
DOI：
10.1073/pnas.2109256118
发表时间：
2021-12-28
影响因子：
11.1
作者：
Dilliard, Sean A.;Cheng, Qiang;Siegwart, Daniel J.
通讯作者：
Siegwart, Daniel J.
影响因子：
17.1
作者：
Elia, Uri;Ramishetti, Srinivas;Peer, Dan
通讯作者：
Peer, Dan
影响因子：
15
作者：
Chen, Delai;Love, Kevin T.;Anderson, Daniel G.
通讯作者：
Anderson, Daniel G.