Strategies to Antagonize miRNA Functions In Vitro and In Vivo

Abstract

miRNAs are a class of short noncoding RNAs that regulate gene expression post-transcriptionally. Diseased tissues have altered miRNA expression patterns, which could provide potential therapeutic targets. Introducing chemically engineered antisense oligonucleotides to cells can silence upregulated miRNAs. Successful miRNA inhibition can be assessed directly by quantitative reverse transcription PCR or northern blot, or indirectly by measuring de-repression of target genes or using reporter assays. In this review, we will discuss the design of chemically modified antisense oligonucleotides (anti-miRNA), in vivo delivery of anti-miRNA to inhibit disease-related miRNAs and the development of nanoparticle-based anti-miRNA delivery systems. In particular, we will focus on interfering nanoparticles that we designed for in vivo delivery of chemically modified anti-miRNA-122 in mice.

Keywords::

• anti-miRNA oligonucleotides
• chemical modification
• interfering nanoparticle
• in vivo anti-miRNA delivery
• miRNA inhibition

Financial & competing interests disclosure

This research has been supported in part by grants from the NIH to TM Rana. 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.

Additional information

Funding

This research has been supported in part by grants from the NIH to TM Rana. 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.