Abstract：
Nanodevices that function in specific organs or cells are one of the ultimate goals of synthetic biology. The recent progress in DNA nanotechnology such as DNA origami has allowed us to construct nanodevices to deliver a payload (e.g., drug) to the tumor. However, delivery to specific organs remains difficult due to the fragility of the DNA nanostructure and the low targeting capability of the DNA nanostructure. Here, we constructed tough DNA origami that allowed us to encapsulate the DNA origami into lipid-based nanoparticles (LNPs) under harsh conditions (low pH), harnessing organ-specific delivery of the gene of interest (GOI). We found that DNA origami-encapsulated LNPs can increase the functionality of payload GOIs (mRNA and siRNA) inside mouse organs through the contribution from different LNP structures revealed by cryogenic electron microscope (Cryo-EM). These data should be the basis for future organ-specific gene expression control using DNA origami nanodevices.
摘要：
在特定器官或细胞中起作用的纳米装置是合成生物学的最终目标之一。DNA纳米技术的最新进展，如DNA折纸，使我们能够构建纳米设备来递送有效载荷(例如，药物）对肿瘤。然而,由于DNA纳米结构的脆性和DNA纳米结构的低靶向能力,递送至特定器官仍然困难。这里,我们构建了艰难的DNA折纸，使我们能够在苛刻的条件（低pH）下将DNA折纸封装到基于脂质的纳米颗粒（LNP）中，利用目的基因（GOI）的器官特异性递送。我们发现，DNA折纸封装的LNP可以通过低温电子显微镜（Cryo-EM）揭示的不同LNP结构的贡献来增加小鼠器官内有效负载GOI（mRNA和siRNA）的功能。这些数据应该是未来使用DNA折纸纳米设备进行器官特异性基因表达控制的基础。
