Research ArticleMetabolic Syndrome

Pharmacological Inhibition of a MicroRNA Family in Nonhuman Primates by a Seed-Targeting 8-Mer AntimiR

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Science Translational Medicine  20 Nov 2013:
Vol. 5, Issue 212, pp. 212ra162
DOI: 10.1126/scitranslmed.3006840

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Little AntimiR Packs a Double Punch

MicroRNAs (miRNAs) are a type of noncoding RNA that are about 22 nucleotides in length and affect a variety of cellular functions, including normal development and metabolism. These RNAs have also been implicated in many different diseases. Targeted inhibition of miRNAs can be achieved with antimiRs—RNA segments with complementary sequences to miRNAs of interest, which can bind and specifically inhibit their target miRNAs.

In humans, miRNAs called miR-33a and miR-33b help control the homeostasis of cholesterol and other lipids, which are associated with cardiovascular disease. To inhibit both of these miRNAs at the same time, Rottiers and colleagues created an unusually short antimiR, only 8 nucleic acids in length, which targets the common portion of both miR-33a and miR-33b. They had tested it in mammalian cells and in mice, and now also confirmed that this short antimiR can be used in nonhuman primates. The authors demonstrated that their antimiR is safe in obese, insulin-resistant nonhuman primates, and that it increases high-density lipoprotein cholesterol.

Additional studies will be necessary to learn more about the effects of this 8-mer antimiR on different parameters of metabolism, and to determine how it affects clinical outcomes, such as the risk of death from cardiovascular disease. Nevertheless, this work suggests that miRNA-based approaches could be specifically tailored and potentially safe for patient use, providing an alternative to standard pharmaceutical interventions.

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