Ultrasound Assisted Exosomal Delivery of Tissue Responsive mRNA for Enhanced Efficacy and Minimized Off-Target Effects.

ABSTRACT: Exosome-mediated nucleic acids delivery has been emerging as a promising strategy for gene therapy. However, the intrinsic off-target effects due to non-specific uptake of exosomes by other tissues remain the big hurdle for clinical application. In this study, we aimed to enhance the efficacy and minimize the off-target effects by simultaneously encapsulating engineered mRNA translationally activated by tissue-specific microRNA (miRNA) and increasing targeted delivery efficiency via ultrasound-targeted microbubble destruction (UTMD). Briefly, the upstream of interest transcript was engineered to harbor an internal ribosome entry site (IRES) modified with two miRNA recognition sites. In vitro reporter experiments revealed that the engineered mRNA could be encapsulated into exosomes and can

SUBMITTER: Sun W 

PROVIDER: S-EPMC7182664 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature