Work

Managing MicroRNAs with Vector-Encoded Decoy-Type Inhibitors

Year: 2013

Type: review

Abstract: A rapidly growing understanding of the complex circuitry of microRNA (miRNA)-mediated gene regulation is attracting attention to miRNAs as new drug targets. Targeted miRNA suppression is achieved in a sequence-specific manner by antisense RNA "decoy" molecules. Such synthetic miRNA inhibitors have reached the clinic with remarkable pace and may soon appear as new therapeutic modalities in several diseases. Shortcomings, however, include high production costs, the requirement for repeated administration, and difficulty achieving tissue-specific delivery. With the many recent landmark achievements in clinical gene therapy, new and refined vector-encoded miRNA suppression technologies are attractive for many applications, not least as tools in innumerable daily studies of miRNA biology in laboratories worldwide. Here, we provide an overview of the strategies that have been used to adapt vector-encoded inhibitors for miRNA suppression and discuss advantages related to spatiotemporal and long-term miRNA attenuation. With the remarkable new discovery of miRNA management by naturally occurring circular RNAs, RNA circles generated by trans-splicing mechanisms may prove to be well-suited carriers of decoy-type miRNA inhibitors. The community will aspire to combine circles with high-affinity miRNA decoy methodologies, and such "vectorized" RNA circles may represent new solid ways to deliver miRNA inhibitors, perhaps even with therapeutic applications.

Source: Molecular Therapy

DOI: 10.1038/mt.2013.113

Authors: Rasmus O Bak, Anne Kruse Hollensen, Jacob Giehm Mikkelsen

Institution: Aarhus University

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500