miRNA Knockdown in Primates
Yesterday in Nature was a really exciting paper on miRNA-targeting therapeutics: Locked-Nucleic Acid-based knockdown of miRNAs in vivo!
microRNAs (miRNAs) are really tiny regulatory RNAs (about 22 nucleotides long); efficient, specific hybridization would normally require something much longer. Recently, though, the use of “locked nucleic acids” has become more popular. These are RNA analogues that have an extra bridge in the ribose sugar, making oligos of them rigid. Entropically, this greatly enhances binding of the LNAs to the RNAs, which means that one can use them for things like in situ hybridization much more easily and specifically! Not only that, but the use of LNAs instead of normal RNAs means that the half-lives of the oligos become much longer, similar to what one would see with morpholinos.
The authors injected LNAs into monkeys in order to target miR-122, which regulates cholesterol metabolism (among other things). They managed to effectively silence the miR-122 and they showed a drop in cholesterol levels!
Very exciting stuff!
