MicroRNA (miRNA) Inhibitors are steric blocking oligonucleotides that hybridize to mature miRNAs, inhibiting their function. IDT® miRNA Inhibitors are oligonucleotides comprised of 2'-O-methyl residues with ZEN™ modifications at or near the ends. Incorporating 2'-O-methyl residues confers resistance to endonuclease degradation and increases binding affinity to RNA targets, while the ZEN modification blocks exonuclease degradation and further increases binding affinity.
Features
- High potency provides effective inhibition of miRNA function in vitro at low nanomolar concentrations
- High specificity to ensure that the desired target is knocked down
- Uniform design for all miRNAs provides simplicity
- Nontoxic to mammalian cells
- Easy ordering
The standard method for inhibiting microRNA (miRNA) function is by steric blocking, using an oligonucleotide that is perfectly complementary to the mature miRNA target. These inhibitors form a duplex with the miRNA guide strand and prevent the miRNA from binding to its intended target.
For effective miRNA inhibition, the binding affinity between the oligo inhibitor and the miRNA must be significantly higher than that between miRNA guide strand and passenger strand. The miRNA inhibitor must be capable of binding to the miRNA guide strand either in single-stranded form or when bound to an Argonaute protein in the miRNA-induced silencing complex (miRISC). The inhibitor should also be capable of displacing the natural passenger strand in double-stranded miRNA.
Adding a 2′ modification to ribose sugars in the RNA backbone can increase Tm and confer resistance to endonucleases [1]. 2′-O-Methyl RNA (2′OMe) is a naturally-occurring, nontoxic nucleic acid with a high binding affinity for RNA that provides the required resistance to mammalian endonucleases. Adding ZEN™ modifications to the termini of 2′OMe-modified oligonucleotides further increases the binding affinity of the miRNA inhibitors and confers resistance to exonucleases [1].
References
- Lennox, KA, Owczarzy R, et al. (2013) Improved performance of anti-miRNA oligonucleotides using a novel non-nucleotide modifier. Mol Ther Nucleic Acids, 2:e117.
Further Reading
Lennox KA, Behlke MA. (2011) Chemical modification and design of anti-miRNA oligonucleotides.Gene Ther, 18:1111–1120.
Lennox KA, Behlke MA. (2010) A direct comparison of anti-microRNA oligonucleotide potency. Pharm. Res, 27(9):1788–1799.
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