Genes, Cells, and MiRNAs

Abstract

Novel methods to treat HF include gene, cell and microRNA  delivery. There have been few gene therapy trials in HF. The CUPID I and II trials with AAV1.SERCA2a showed unconvincing results. The STOP-HF trial using direct intra-myocardial injection of a non-integrating plasmid vector carrying stromal cell-derived factor-1 showed no clinical effects and the AC6 gene transfer trial used IC infusion of escalating doses of Ad5.hAC6 was similarly negative. Despite high hopes stem cell trials to date in HF have not shown convincing clinical benefits. More recent clinical trials in this area have investigated the injection of cell stimulating paracrine factors (peptides, small molecules, hormone-like molecules) without actual cell delivery. Micro-RNA’s (miRNAs) are small non-coding RNA strands, comprising 19-25 nucleotides, that have a distinct signalling role and a various patterns of expression in ischaemic myocardium, hypertrophy, cardiomyopathies, and overt HF. They act at the post-transcriptional regulation level. Numerous novel miRNAs have been discovered, and their in-depth role has been characterised. miRNAs can serve as therapeutic substances or therapeutic targets in a range of cardiovascular diseases.   Clinical trials are likely in the near future.