No abstract

The intrinsic ability of neurogenesis after stroke has been proven weak, which results in insufficient repair of injury in the nerve system. Recent studies suggest multiple microRNAs (miRNAs) are involved in the neuroremodeling process. Targeted miRNAs delivery for amplification of neurogenesis is promising in promoting the prognosis after ischemia. Here, we showed that modified exosomes, with rabies virus glycoprotein (RVG) fused to exosomal protein lysosome-associated membrane glycoprotein 2b (Lamp2b), could efficiently deliver miR-124 to the infarct site. Systemic administration of RVG-exosomes loaded with miR-124 promoted cortical neural progenitors to obtain neuronal identity and protect against ischemic injury by robust cortical neurogenesis. Our study suggests that RVG-exosomes can be utilized therapeutically for the targeted delivery of gene drugs to the brain, thus having great potential for clinical applications.

No abstract

In vitro and in vivo delivery of RNAs of interest holds promise for gene therapy. Recently, exosomes are considered as a kind of rational vehicle for RNA delivery, especially miRNA and/or siRNA, while the loading efficiency is limited. In this study, we engineered the exosomes for RNA loading by constructing a fusion protein in which the exosomal membrane protein CD9 was fused with RNA binding protein, while the RNA of interest either natively harbors or is engineered to have the elements for the binding. By proof-of-principle experiments, we here fused CD9 with HuR, an RNA binding protein interacting with miR-155 with a relatively high affinity. In the exosome packaging cells, the fused CD9-HuR successfully enriched miR-155 into exosomes when miR-155 was excessively expressed. Moreover, miR-155 encapsulated in the exosomes in turn could be efficiently delivered into the recipient cells and recognized the endogenous targets. In addition, we also revealed that the CD9-HuR exosomes could enrich the functional miRNA inhibitor or CRISPR/dCas9 when the RNAs were engineered to have the AU rich elements. Taken together, we here have established a novel strategy for enhanced RNA cargo encapsulation into engineered exosomes, which in turn functions in the recipient cells.

Background & Aims-Colon cancer is one of the best-understood neoplasms from a genetic perspective, yet it remains the second most common cause of cancer-related death. Posttranscriptional regulation mediated by RNA binding proteins or microRNAs coordinately targets multiple genes, holding promise involved in colon cancer initiation and development. Here we studied the role of RNA binding protein QKI in colon cancer.