miRNA inhibition in vivo? - (Jul/15/2008 )
Has anyone had experience with miRNA inhibition in vivo? Eurogentec has a miRNA inhibitor that is cholesterol conjugated (Krutzfeldt 2007) that they say can be used in vivo, but I'm just wondering if anyone's had experience with it (or any others) before I cough up the money... Thanks.
A Vivo-Morpholino targeting the miRNA should do the trick.
Vivo-Morpholinos can enter cells of adult mammals from the blood and interact with RNA targets. We have seen no publications using Vivo-Morpholinos with miRNA targets, but bare (unconjugated) Morpholino oligos have been used and published blocking miRNA activity, blocking miRNA maturation and protecting miRNA targets on mRNA.
Paper on Vivo-Morpholinos:
Li YF, Morcos PA. Design and Synthesis of Dendritic Molecular Transporter that Achieves Efficient in Vivo Delivery of Morpholino Antisense Oligo. Bioconjug Chem. 2008 Jun 20. [Epub ahead of print]
Paper on blocking miRNA maturation with Morpholino oligos:
Kloosterman WP, Lagendijk AK, Ketting RF, Moulton JD, Plasterk RH. Targeted Inhibition of miRNA Maturation with Morpholinos Reveals a Role for miR-375 in Pancreatic Islet Development. PLoS Biol. 2007 Jul 24;5(8):e203 [Epub ahead of print]
Paper using Morpholinos to block mRNA translation, block miRNA activity & maturation and using Morpholinos to protect miRNA target sites:
Li N, Flynt AS, Kim HR, Solnica-Krezel L, Patton JG. Dispatched Homolog 2 is targeted by miR-214 through a combination of three weak microRNA recognition sites. Nucleic Acids Res. 2008 Jun 26. [Epub ahead of print]
Web pages at Gene Tools describing blocking miRNA with Morpholinos (and reference list):
Web pages at Gene Tools describing Vivo-Morpholinos: