Extracellular vesicle‐mediated delivery of circDYM alleviates CUS‐induced depressive‐like behaviours

• DOI: 10.1002/jev2.12185
• Publication Date: 2022-01-14T04:39:58Z
• Authors: Xiaoyu Yu; Ying Bai; Bing Han; Minzi Ju; Tianci Tang; Ling Shen; Mingyue Li; Li Yang; Zhao Zhang; Guoku Hu; Jie Chao; Yuan Zhang; Honghong Yao
• Keywords: Extracellular Vesicles; Extracellular vesicles

Abstract Major depressive disorder (MDD) is the most prevalent psychiatric worldwide and severely limits psychosocial function quality of life, but no effective medication currently available. Circular RNAs (circRNAs) have been revealed to participate in MDD pathological process. Targeted delivery circRNAs without blood‐brain barrier (BBB) restriction for remission represents a promising approach antidepressant therapy. In this study, RVG‐circDYM‐extracellular vesicles (RVG‐circDYM‐EVs) were engineered target preferentially transfer circDYM brain, effect on process chronic unpredictable stress (CUS) mouse model depression was investigated. The results showed that RVG‐circDYM‐EVs successfully purified by ultracentrifugation from overexpressed HEK 293T cells, characterization demonstrated terms size, morphology specific markers. Beyond demonstrating proof‐of‐concept an RNA drug technology, we observed systemic administration efficiently delivered alleviated CUS‐induced depressive‐like behaviours, discovered notably inhibited microglial activation, BBB leakiness peripheral immune cells infiltration, attenuated astrocyte disfunction induced CUS. CircDYM can bind mechanistically transcription factor TAF1 (TATA‐box binding protein associated 1), resulting decreased expression its downstream genes with consequently suppressed neuroinflammation. Taken together, our findings suggest extracellular vesicle‐mediated treatment clinical applications.