**6. miRNA therapeutics: strategies**

There are at least two main strategies to target miRNA expression for prevention and potential treatment of disease. The first strategies is the use of oligonucleotides or virus-based constructs to either directly block the expression of a diseaseassociated signature miRNA or to directly substitute for the loss of expression of the miRNA. The second strategies is indirectly employing drugs to alter miRNA expression by targeting their transcription and processing. Blocking miRNA expression can be achieved by the use of antisense oligonucleotides, miRNA sponges, miRNAmask and small RNA inhibitors. Restoring downregulated miRNA expression can be achieved by using synthetic miRNA (miRNA mimic) or by inserting genes coding for miRNA into viral constructs. At the transcriptional level, small-molecule miRNA inhibitors can be employed to prevent the transitions from DNA transcript to pri-miRNA and pre-miRNA. Antisense oligonucleotides can be employed at the mature miRNA level to induce degradation or revert the mature miRNA into a duplex form with the antisense oligonucleotide. At the functional level, miRNA masks can bind complementarily to the 3' UTR region of target mRNA, competing for bindings with endogenous miRNAs for the specific target. miRNA sponges can be employed to bind target miRNA via complementary mRNA binding sites, decreasing expression levels of target miRNAs (see **Figure 1**).
