Rackley Lauren, Stewart Jaimie Marie, Salotti Jacqueline, Krokhotin Andrey, Shah Ankit, Halman Justin R, Juneja Ridhima, Smollett Jaclyn, Lee Lauren, Roark Kyle, Viard Mathias, Tarannum Mubin, Vivero-Escoto Juan, Johnson Peter F, Dobrovolskaia Marina A, Dokholyan Nikolay V, Franco Elisa, Afonin Kirill A
Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
Department of Bioengineering, University of California, Riverside, CA 92521, USA.
Adv Funct Mater. 2018 Nov 28;28(48). doi: 10.1002/adfm.201805959. Epub 2018 Oct 9.
RNA is a versatile biomaterial that can be used to engineer nanoassemblies for personalized treatment of various diseases. Despite promising advancements, the design of RNA nanoassemblies with minimal recognition by the immune system remains a major challenge. Here, an approach is reported to engineer RNA fibrous structures to operate as a customizable platform for efficient coordination of siRNAs and for maintaining low immunostimulation. Functional RNA fibers are studied in silico and their formation is confirmed by various experimental techniques and visualized by atomic force microscopy (AFM). It is demonstrated that the RNA fibers offer multiple advantages among which are: i) programmability and modular design that allow for simultaneous controlled delivery of multiple siRNAs and fluorophores, ii) reduced immunostimulation when compared to other programmable RNA nanoassemblies, and iii) simple production protocol for endotoxin-free fibers with the option of their cotranscriptional assembly. Furthermore, it is shown that functional RNA fibers can be efficiently delivered with various organic and inorganic carriers while retaining their structural integrity in cells. Specific gene silencing triggered by RNA fibers is assessed in human breast cancer and melanoma cell lines, with the confirmed ability of functional fibers to selectively target single nucleotide mutations.
RNA是一种多功能生物材料，可用于构建纳米组装体，以实现对各种疾病的个性化治疗。尽管取得了令人鼓舞的进展，但设计出能被免疫系统最少识别的RNA纳米组装体仍是一项重大挑战。在此，报道了一种构建RNA纤维结构的方法，该结构可作为一个可定制平台，用于高效协调小干扰RNA（siRNA）并保持低免疫刺激。对功能性RNA纤维进行了计算机模拟研究，并用各种实验技术证实了其形成过程，还通过原子力显微镜（AFM）进行了可视化观察。结果表明，RNA纤维具有多种优势，其中包括：i）可编程性和模块化设计，可同时控制多种siRNA和荧光团的递送；ii）与其他可编程RNA纳米组装体相比，免疫刺激降低；iii）生产无内毒素纤维的简单方案，可选择共转录组装。此外，研究表明，功能性RNA纤维可以通过各种有机和无机载体有效递送，同时在细胞中保持其结构完整性。在人乳腺癌和黑色素瘤细胞系中评估了RNA纤维引发的特异性基因沉默，证实了功能性纤维能够选择性靶向单核苷酸突变。
