Abstract
miRNAs are small non-coding RNAs (ncRNAs), which regulate gene expression. Here, the authors describe the contribution of miRNAs to cardiac biology and disease. They discuss various strategies for manipulating miRNA activity including antisense oligonucleotides (antimiRs, blockmiRs), mimics, miRNA sponges, Tough Decoys and miRNA mowers. They review developments in chemistries (e.g., locked nucleic acid) and modifications (sugar, ‘ZEN’, peptide nucleic acids) and miRNA delivery tools (viral vectors, liposomes, nanoparticles, pHLIP). They summarize potential miRNA therapeutic targets for heart disease based on preclinical studies. Finally, the authors review current progress of miRNA therapeutics in clinical development for HCV and cancer, and discuss challenges that will need to be overcome for similar therapies to enter the clinic for patients with cardiac disease.
Acknowledgements
The authors would like to thank members of the Cardiac Hypertrophy Laboratory at Baker IDI for administrative support.
Financial & competing interests disclosure
The authors acknowledge funding support from the National Health and Medical Research Council of Australia (NHMRC). JR McMullen is supported by a NHMRC Senior Research Fellowship (1078985). JR McMullen, RCY Lin and BC Bernardo have collaborated (no financial involvement) with scientists at Santaris Pharma A/S (now Roche Innovation Center), a clinical stage biopharmaceutical company that develops miRNA-targeted therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.