Sun Dawei, Li Yize, Yin Xiaoxuan, Fan Yali, Liu Jing, Wang Yaxin, Liu Xinyu, Bai Guijie, Li Ke, Shi Yanyan, Liu Peiyuan, Zhang Yingying, Wang Hanjie
School of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin University, Tianjin 300072, China.
School of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, China.
ACS Nano. 2024 Dec 31;18(52):35296-35309. doi: 10.1021/acsnano.4c11412. Epub 2024 Dec 18.
Delivery systems play a crucial role in RNA therapy. However, the current RNA delivery system involves complex preparation and transport processes, requiring RNA preassembly , transportation at low temperatures throughout, and possibly multiple injections for improved therapeutic efficacy. To address these challenges, we developed a simple and efficient RNA delivery system. This system only requires the injection of engineered bacteria, which serve as "cell factories" for continuous production of the target RNA. The RNA can self-assemble with engineered bacteria's outer membrane vesicles (OMVs), facilitating RNA delivery. Experimental results demonstrated that this system allowed effective delivery with excellent stability and continuity for various types of RNA, including mRNA, miRNA, and siRNA. And the relative abundance of target RNA in the OMVs was 10-10 times higher than that in the mock group. We took the delivery of PD-L1 siRNA for tumor treatment as an example and found that this system could effectively downregulate the gene expression of PD-L1 by approximately twofold. Notably, a single injection of engineered bacteria achieved a significant tumor suppression of 49.37% . This research provides promising insights into the RNA delivery system for tumor therapy.
递送系统在RNA治疗中起着至关重要的作用。然而，当前的RNA递送系统涉及复杂的制备和运输过程，需要进行RNA预组装，全程低温运输，并且可能需要多次注射以提高治疗效果。为应对这些挑战，我们开发了一种简单高效的RNA递送系统。该系统仅需注射工程菌，这些工程菌作为“细胞工厂”持续生产目标RNA。RNA可与工程菌的外膜囊泡（OMV）自组装，促进RNA递送。实验结果表明，该系统能够对包括mRNA、miRNA和siRNA在内的各类RNA进行有效递送，且具有出色的稳定性和连续性。并且OMV中目标RNA的相对丰度比对照组高10至10倍。我们以递送PD-L1 siRNA用于肿瘤治疗为例，发现该系统可有效下调PD-L1的基因表达约两倍。值得注意的是，单次注射工程菌实现了49.37%的显著肿瘤抑制效果。这项研究为肿瘤治疗的RNA递送系统提供了有前景的见解。
