Researchers have effectively silenced microRNAs (miRNAs) in monkeys for the first time, targeting a liver-specific miRNA and reducing blood cholesterol as a result. The research is the first demonstration of miRNA silencing in primates and supports the potential of new nucleic-acid-based therapeutics, as many disease-associated genes are regulated by miRNAs.
Previous work has demonstrated that short interfering RNAs can be administered in primates to reduce expression from select messenger RNAs. Sakari Kauppinen and colleagues now show that a therapeutic effect can also be achieved by targeting miRNAs; their results are reported online in Nature. The authors synthesized a short DNA sequence composed of modified nucleotides that had complementarity to a miRNA that regulates a gene involved in cholesterol metabolism. Injection of this oligonucleotide led to a reduction in serum cholesterol without detectable toxicity in the monkeys.
The research is an important step in understanding the functions of miRNAs and in the future development of oligonucleotide-based therapeutics.
Sakari Kauppinen (Santaris Pharma, Hørsholm, Denmark)
Abstract available online.
(C) Nature press release.
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