Virus Mimetic Framework DNA as a Non-LNP Gene Carrier for Modulated Cell Endocytosis and Apoptosis,ACS Nano

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Virus Mimetic Framework DNA as a Non-LNP Gene Carrier for Modulated Cell Endocytosis and Apoptosis
ACS Nano ( IF 15.8 ) Pub Date : 2023-01-24 , DOI: 10.1021/acsnano.2c09772
Qian Shi ₁ , Yuanyuan Wu ₁ , Yunyun Xu ₁ , Min Bao ₁ , Xiao Chen ₁ , Kui Huang ₁ , Qiulan Yang ₁ , Yang Yang ₁

Affiliation

Mimicking the size and shape of spherical viruses, we constructed a soccer-ball shaped virus-inspired DNA origami (ViDO) framework as a programmable non-LNP (lipid nanoparticle) gene carrier. The DNA framework was decorated with precisely controlled recognition molecules outside and loaded with adequate genetic molecules inside. Five variants were constructed to systematically investigate their cell uptake and modulated gene silencing efficiency. Cellular uptake was enhanced with an increasing number of aptamers, while with a median number of aptamer supply, dispersed distribution performed better than the clustered pattern. Intriguingly, the transfection efficiency was maximized using the ViDO with clustered five aptamers, which exhibited a competitive RNA silencing effect induced by Lipo2000 with low cytotoxicity. Our results revealed the effects of aptamer distribution patterns on endocytosis and transfection, thus providing a programmable platform for meticulous optimization of the gene delivery system.

中文翻译：

病毒模拟框架 DNA 作为非 LNP 基因载体用于调节细胞内吞和凋亡

模仿球形病毒的大小和形状，我们构建了一个足球形病毒启发的 DNA 折纸 (ViDO) 框架作为可编程的非 LNP（脂质纳米颗粒）基因载体。DNA框架外部装饰有精确控制的识别分子，内部装载了足够的遗传分子。构建了五个变体以系统地研究它们的细胞摄取和调节的基因沉默效率。随着适体数量的增加，细胞摄取得到增强，而适体供应的中位数，分散分布比聚集模式表现更好。有趣的是，使用具有聚集的五个适体的 ViDO 可以最大限度地提高转染效率，这表现出由 Lipo2000 诱导的具有低细胞毒性的竞争性 RNA 沉默效应。

更新日期：2023-01-24

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