Novel fusion peptide-mediated siRNA delivery using self-assembled nanocomplex.
Novel fusion peptide-mediated siRNA delivery using self-assembled nanocomplex.
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DOI：
10.1186/s12951-021-00791-x
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发表时间：
2021-02-12
影响因子：
10.2
通讯作者：
Hwang BH
中科院分区：
文献类型：
--
作者：
Ryu YC;Kim KA;Kim BC;Wang HD;Hwang BH
使用siRNA进行基因沉默可能是一种新的有效策略，可以在遗传水平上治疗许多无法治愈的疾病，包括癌症和病毒感染。使用siRNA的治疗基本上需要一种有效和安全的方法将siRNA递送到细胞中，同时保持其稳定性。因此，我们设计了新的协同融合肽，即SPACE和低精氨酸。在新型融合肽和sirna中，纳米复合物在体外增强了sirna的细胞摄取和基因沉默作用，在体内改善了sirna的保留和基因沉默作用。低精氨酸可以静电吸引sirna形成稳定的自组装纳米复合物，SPACE肽可以通过氢键与细胞膜相互作用。因此，使用融合肽的纳米复合物通过脂质载体介导的内吞途径，对甘油醛3-磷酸脱氢酶（GAPDH）的细胞摄取和基因沉默表现出明显的改善，特别是对皮肤的HDFn细胞，所有融合肽都具有生物相容性。此外，瘤内注射纳米复合物增加了sirna在肿瘤部位的滞留时间。最后，纳米复合物在体内表现出显著的基因沉默作用，没有明显的组织损伤和免疫细胞浸润。新的纳米复合物策略可以成为一个安全有效的平台，将sirna递送到细胞和组织中，通过基因沉默治疗各种靶疾病。
Gene silencing using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine. Among the novel fusion peptides and siRNAs, nanocomplexes have enhanced cellular uptake and gene silencing effect in vitro and improved retention and gene silencing effects of siRNAs in vivo. Oligoarginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased retention time of siRNAs at the site of the tumor. Finally, nanocomplexes demonstrated significant in vivo gene silencing effect without overt tissue damage and immune cell infiltration. The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene silencing.
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影响因子：
--
作者：
Chiu, YL;Ali, A;Rana, TM
通讯作者：
Rana, TM
影响因子：
3.7
作者：
Langlet-Bertin, Berangere;Leborgne, Christian;Kichler, Antoine
通讯作者：
Kichler, Antoine
DOI：
10.1016/j.jconrel.2015.09.066
发表时间：
2015-11-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Sarett SM;Nelson CE;Duvall CL
通讯作者：
Duvall CL
影响因子：
16.1
作者：
Tai W;Gao X
通讯作者：
Gao X
影响因子：
14
作者：
Sarett SM;Werfel TA;Chandra I;Jackson MA;Kavanaugh TE;Hattaway ME;Giorgio TD;Duvall CL
通讯作者：
Duvall CL