Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism.
Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism.
复制标题
改变电荷可释放的转运蛋白可以在体外增强mRNA的递送，并在体内表现出体内递送。
DOI：
10.1038/s41467-023-42672-x
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发表时间：
2023-11-01
影响因子：
16.6
通讯作者：
Wender PA
中科院分区：
文献类型：
--
作者：
Li Z;Amaya L;Pi R;Wang SK;Ranjan A;Waymouth RM;Blish CA;Chang HY;Wender PA
许多新兴生物医学技术的发展需要引入更有效和更具选择性的 mRNA 传递系统，包括开发预防性和治疗性疫苗、癌症免疫疗法和基因组编辑策略。虽然聚合物和寡聚物已成为有前途的 mRNA 递送系统，但它们在难以转染的细胞（如原代 T 淋巴细胞）中的功效通常受到限制，而且它们的细胞和器官向性也受到限制。为了解决这些问题，人们对 mRNA 递送系统的各种脂质和阳离子成分的结构筛选给予了相当多的关注。在这里，我们公开了一类改变电荷的可释放转运蛋白（CART），其与之前的 CART 的不同之处在于其 β-酰胺基碳酸酯主链（bAC）和侧链间距。这些 bAC-CART 在体外表现出增强的原代 T 淋巴细胞 mRNA 转染，并增强体内蛋白质表达，并具有高度选择性的脾向性，支持其作为有效的聚阴离子递送系统的更广泛的治疗用途。聚合物有望用于 mRNA 递送，但在难以转染的细胞中效果有限。在此，作者报告了改变电荷的可释放转运蛋白，可改善原代 T 淋巴细胞中的 mRNA 转染，并增强体内选择性蛋白质表达。
The introduction of more effective and selective mRNA delivery systems is required for the advancement of many emerging biomedical technologies including the development of prophylactic and therapeutic vaccines, immunotherapies for cancer and strategies for genome editing. While polymers and oligomers have served as promising mRNA delivery systems, their efficacy in hard-to-transfect cells such as primary T lymphocytes is often limited as is their cell and organ tropism. To address these problems, considerable attention has been placed on structural screening of various lipid and cation components of mRNA delivery systems. Here, we disclose a class of charge-altering releasable transporters (CARTs) that differ from previous CARTs based on their beta-amido carbonate backbone (bAC) and side chain spacing. These bAC-CARTs exhibit enhanced mRNA transfection in primary T lymphocytes in vitro and enhanced protein expression in vivo with highly selective spleen tropism, supporting their broader therapeutic use as effective polyanionic delivery systems. Polymers are promising for mRNA delivery, but can have limited efficacy in hard to transfect cells. Here, the authors report charge-altering releasable transporters for improved mRNA transfection in primary T-lymphocytes and enhanced and selective protein expression in vivo.
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DOI：
10.1158/1078-0432.ccr-18-0432
发表时间：
2019-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Majzner RG;Theruvath JL;Nellan A;Heitzeneder S;Cui Y;Mount CW;Rietberg SP;Linde MH;Xu P;Rota C;Sotillo E;Labanieh L;Lee DW;Orentas RJ;Dimitrov DS;Zhu Z;Croix BS;Delaidelli A;Sekunova A;Bonvini E;Mitra SS;Quezado MM;Majeti R;Monje M;Sorensen PHB;Maris JM;Mackall CL
通讯作者：
Mackall CL
影响因子：
82.9
作者：
Long, Adrienne H.;Haso, Waleed M.;Shern, Jack F.;Wanhainen, Kelsey M.;Murgai, Meera;Ingaramo, Maria;Smith, Jillian P.;Walker, Alec J.;Kohler, M. Eric;Venkateshwara, Vikas R.;Kaplan, Rosandra N.;Patterson, George H.;Fry, Terry J.;Orentas, Rimas J.;Mackall, Crystal L.
通讯作者：
Mackall, Crystal L.
影响因子：
6.2
作者：
Benner, Nancy L.;Near, Katherine E.;Wender, Paul A.
通讯作者：
Wender, Paul A.
DOI：
10.1073/pnas.1810002115
发表时间：
2018-09-25
影响因子：
11.1
作者：
Haabeth, Ole A. W.;Blake, Timothy R.;Levy, Ronald
通讯作者：
Levy, Ronald
DOI：
10.1073/pnas.2302191120
发表时间：
2023-05-16
影响因子：
11.1
作者：
Amaya, Laura;Grigoryan, Lilit;Li, Zhijian;Lee, Audrey;Wender, Paul A.;Pulendran, Bali;Chang, Howard Y.
通讯作者：
Chang, Howard Y.