Mirna-Based Therapies: Strategies and Delivery Platforms for Oligonucleotide and Non-Oligonucleotide Agents

Abstract

The discovery of miRNAs as important regulatory agents for gene expression has expanded the therapeutic opportunities for oligonucleotides. In contrast to siRNA, miRNA-targeted therapy is able to influence not only a single gene, but entire cellular pathways or processes. It is possible to supplement downregulated or non-functional miRNAs by synthetic oligonucleotides, as well as alleviating effects caused by overexpression of malignant miRNAs through artificial antagonists, either oligonucleotides or small molecules. Chemical oligonucleotide modifications together with an efficient delivery system seem to be mandatory for successful therapeutic application. While miRNA-based therapy benefits from the decades of research spent on other therapeutic oligonucleotides, there are some specific challenges associated with miRNA therapy, mainly caused by the short target sequence. The current status and recent progress of miRNA-targeted therapeutics is described and future challenges and potential applications in treatment of cancer and viral infections are discussed.

Gene Set Enrichment Analysis (GSEA) of Upregulated Genes in Cocaine Addiction Reveals miRNAs as Potential Therapeutic Agents

“…Mitigating the effects exerted by overexpression of malignant miRNAs is possible through the application of artificial antagonists such as oligonucleotides or other small molecules. It is also possible to supplement miRNAs through the use of synthetic oligonucleotides [36]. In the case of current study, the miRNAs which were found to influence the transcription of upregulated genes in cocaine addiction can be supplemented so that they can negatively regulate those genes and thus reduce the addictive effects.…”

Gene Set Enrichment Analysis (GSEA) of Upregulated Genes in Cocaine Addiction Reveals miRNAs as Potential Therapeutic Agents

“…Mitigating the effects exerted by overexpression of malignant miRNAs is possible through the application of artificial antagonists such as oligonucleotides or other small molecules. It is also possible to supplement miRNAs through the use of synthetic oligonucleotides [21]. In the case of current study, the miRNAs which were found to influence the transcription of upregulated genes in cocaine addiction can be supplemented so that they can negatively regulate those genes and thus reduce the addictive effects of cocaine.…”

Therapeutic Oligonucleotides with Polyethylene Glycol Modifications

“…Through their complex, fine-tuned post-transcriptional gene regulation, miRNAs play an important role in the initiation and progression of tumors [21], cardiovascular diseases [22] and other disorders. Since the inception of the role of miRNAs in cancer in 2002, research efforts have mainly been focused on their biological basis, dysregulation in diseases, but also the potential therapeutic value of miRNAs.…”