Cell-Selective Gene Editing

Competitive Advantages:

•     Reduced toxicity
•     High flexibility
•     Ability to edit multiple genes and target multiple cell types

Summary:

Modified mRNA-based therapeutics hold great promise for numerous untreatable diseases. The potential advantages of modified mRNA biomolecules include reduced toxicity, decreased activation of the innate immune pathway, and improved translation in virtually all cell types, including non-dividing cells by circumventing nuclear localiza-tion. Additionally, modified mRNA provides enormous flexibility with respect to production and application, because any protein with a known sequence can be encoded and expressed. Lastly, modified mRNA can be produced rapidly in a cell-free, cost-effective manner. While modified mRNA presents an intriguing therapeutic option for drug delivery and disease treatment, its potential silencing by small interfering RNA or microRNA remains an issue. Our inventors have discovered how microRNA target sequences could be added to guide RNA to selectively edit genes. This strategy is able to achieve cell-selective gene editing, gene activation, or gene sup-pression  and it offers the capacity for multiple genes to be edited, activated or suppressed and multiple cell types to be selectively tar-geted simultaneously in a combination treatment to provide patient-specific therapy. 

miRNA Target Sites of Unmodified mRNA Molecule Increases Silencing in miR-126