What kind of chemical modification for microRNA knockdown experiment?

microRNA probes using mixture of LNA modified 2'-O-Me-RNA (LNA modified antagomirs) have displayed stronger binding to complementary RNA then the corresponding LNA-modified DNA oligos. This property, in combination with increased biostability and pairing specificity, makes such hybrid microRNA  probe the optimal molecules for targeting non-coding RNAs, and the molecules of choice for microRNA research.

For microRNA knock-down experiment, one should be designed with every third or forth base as LNA and the rest as 2'-O-Me-RNA with an overall length of 14-20 nucleotides. The strong and specific RNA binding of such relatively short oligos make them superior for microRNA targeting.

Self-hybridisation is strong. Due to the strong LNA:LNA base pairing it is important to design LNA-modified oligonucleotides with a minimum of self-complementary segments.