Efficient and safe small RNA delivery to macrophage using peptide-based nanocomplex,Biotechnology and Bioengineering

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Efficient and safe small RNA delivery to macrophage using peptide-based nanocomplex
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2021-11-11 , DOI: 10.1002/bit.27988
Yeong Chae Ryu ₁ , Yoo Eun Lee ₁ , Byeong Hee Hwang _{1,

2}

Affiliation

As one of the gene therapies, RNA interference (RNAi) effectively suppresses only specific genes, targeting various diseases in which they are involved. For the successful process of RNAi, efficient and safe delivery of small RNAs, including small interfering RNA and short hairpin RNA, is essential. Herein, an S-R11 fusion peptide, SPACE peptide conjugated with poly-arginine, was introduced to deliver small RNAs into immune cells that are difficult to transfect. This S-R11 peptide stably formed a spontaneous self-assembling nanocomplex through electrostatic attraction and hydrogen bonding with small RNAs. The nanocomplex showed about 5.3-fold better permeation efficiency than the conventional Lipofectamine™ 2000 for RAW 264.7 macrophage cells. Moreover, it induced about 66.2% silencing effect of the target gene in the cells activated with polyinosinic:polycytidylic acid (poly (I:C)). In addition, the cell viability of fusion peptide was ensured even in a concentration range exceeding the concentration used in the nanocomplex. Based on these results, it is expected that the nanocomplex in this study can be used as a new gene delivery system that can overcome the challenge of gene therapies to immune cells.

中文翻译：

使用基于肽的纳米复合物将小 RNA 高效安全地递送至巨噬细胞

作为基因疗法之一，RNA干扰（RNAi）仅有效抑制特定基因，针对它们所涉及的各种疾病。对于 RNAi 的成功过程，高效和安全地传递小 RNA，包括小干扰 RNA 和短发夹 RNA，是必不可少的。在此，引入了一种 S-R11 融合肽，即与聚精氨酸缀合的 SPACE 肽，用于将小 RNA 递送到难以转染的免疫细胞中。这种 S-R11 肽通过静电吸引和与小 RNA 的氢键作用稳定地形成自发的自组装纳米复合物。该纳米复合物对 RAW 264.7 巨噬细胞的渗透效率比传统的 Lipofectamine™ 2000 高约 5.3 倍。此外，它诱导了大约 66 个。用聚肌苷：聚胞苷酸（聚（I：C））激活的细胞中靶基因的2％沉默效应。此外，即使在超过纳米复合物中使用的浓度的浓度范围内，也确保了融合肽的细胞活力。基于这些结果，预计本研究中的纳米复合物可以作为一种新的基因传递系统，克服基因治疗对免疫细胞的挑战。

更新日期：2022-01-11

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