ReviewProgress in microRNA delivery
Graphical abstract
Section snippets
Discovery and action of miRNAs
MicroRNAs (miRNAs) are one of a growing number of non-coding RNA molecules that act within a cell [1], [2]. Noncoding RNAs include miRNA, small interfering RNA (siRNA), ribozymes, among others [3]. Both miRNA and siRNA interact with messenger RNA (mRNA), typically marking the mRNA for degradation as will be described in this review. Ribozymes are RNA molecules that bind to mRNA (or other RNAs) and catalyze the degradation of the RNA with no enzyme [4]. Ribozymes are the only RNAs in this class
MicroRNA therapeutic approaches
Using high-throughput techniques including miRNA microarrays, unique miRNAs expression profiles are being confirmed to mediate critical pathogenic processes in human disease [38], [41], [42]. These findings are rapidly being translated into recommendations targeting miRNA dysregulation. To translate these discoveries to viable therapies, appropriate, stable molecules must be designed and chemically modified poly(nucleic acids) are typically utilized for miRNA therapy. In addition to
Synthetic materials for miRNA and anti-miRNA oligonucleotide delivery
Synthetic materials have demonstrated potential as effective carriers for DNA and siRNA [75], [76], [77], [78], [79]. Under most circumstances, synthetic materials are cationic and condense negatively charged poly(nucleic acid)s through electrostatic interactions. Synthetic delivery systems have considerable advantages over viral-based vector due to the control of their molecular composition, simplified manufacturing, modification and analysis, tolerance for cargo sizes, and relatively lower
Future outlook: challenges and opportunities
Over the last several years, miRNA research has made amazingly rapid progress. But despite this, there is a belief that “RNAi is dead” [143] partly due to the departure from or reduction in emphasis on siRNA and miRNA by the pharmaceutical industry [144]. Few siRNA therapeutics and only two candidate miRNAs, SPC3649 (Santaris Pharma, Horsholm, Denmark) [145], [146], [147], [148], [149], [150], [151] a miR-122 antisense locked nucleic acid, and MRX34 (Mirna Therapeutics, Inc.) [152] a liposomal
Conclusion
Recent developments in the understanding of miRNA have suggested their therapeutic potential. But, the understanding of the biological genesis and activity will be the key to translation of this promising therapeutic class of molecules. Many of the challenges of delivering miRNA are similar, if not equivalent to siRNA and DNA, but some differences exist. The primary differences exist in the specificity of mRNAs that are repressed and the possibility to have promotion of expression directly
Acknowledgments
This review and our original miRNA research was conducted in a facility constructed with support from Research Facilities Improvement Program Grant (RR15482) from the National Centre for Research Resources (NCRR) of the National Institutes of Health (NIH). Our original miRNA delivery research has been funded, in part, by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) award which is also supported by the NCRR (TR000050, RAG).
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