Gap junctional shuttling of miRNA--A novel pathway of intercellular gene regulation and its prospects in clinical application.

The gap junctional exchange of small molecules between adjacent cells is crucial for maintaining tissue homeostasis and for a large number of cellular processes, including differentiation and proliferation. miRNAs represent a novel class of signalling molecules capable of crossing gap junction (GJ) channels, thereby directly affecting gene expression in the recipient cell. Here, we give an overview about the current knowledge on the biological significance of miRNA shuttling in different cell types (e.g. stem cells, cardiac cells, macrophages), which indicates the GJ-dependent transfer of miRNA as a general mechanism for intercellular gene regulation. Notably, shuttling via GJs is superior to exosome-mediated intercellular transfer regarding specificity and efficiency. We further elucidate this mechanism as a promising approach for miRNA delivery in clinical applications. Using a cell-based gap junctional dependent system, in vivo delivery of therapeutic miRNAs might become more efficient compared to systemic delivery methods. We will discuss the advantages of such a delivery system and the challenges that have to be overcome for its successful application in miRNA therapy.