LNA GapmeRs are antisense oligonucleotides (ASOs) 15–16 nucleotides long that provide highly effective mRNA/lncRNA silencing both in vitro and in vivo. These oligos contain a central stretch (“gap”) of DNA monomers flanked by blocks of LNA-modified nucleotides, which enable increased target affinity regardless of GC content. The central DNA gap activates RNase H cleavage of the target RNA upon binding. Designing LNA GapmeRs can be complicated, but our in-house experts can optimize designs for high potency and success.

Fully phosphorothioated backbones provide exceptional resistance to enzymatic degradation, and because they are single stranded, LNA GapmeRs allow strand-specific knockdown of RNAs and minimize off-target effects, due to the lack of a passenger strand. Since LNA GapmeRs act independently of the RNA induced silencing complex (RISC), there are no issues with saturation of RISC. The mRNA knockdown efficacy rivals that of siRNA, so LNA GapmeRs are an excellent alternative for researchers looking for a method that works independently of RISC with no miRNA-like off-target effects.

miRNA mimics simulate the natural functions of endogenous miRNAs and are primarily used in gain-of-function studies. Introducing an miRNA mimic into cells increases the proportion of RISCs containing the guide strand miRNA, enabling assessment of the phenotypic consequences of increased activity and discovery of new miRNA functions. Our miRCURY LNA miRNA Mimics have an innovative design that includes two short, LNA-enhanced complimentary strands that prevent any miRNA-like activity associated with the passenger strands, ensuring that phenotypes observed using these mimics are due to increased activity of the mimicked miRNA only.

miRCURY LNA miRNA Inhibitors are ASOs with perfect sequence complementary to their miRNA targets. When introduced into cell cultures or animal models, they sequester the target miRNA in highly stable heteroduplexes, effectively preventing the miRNA from hybridizing with its normal cellular interaction partners. This specific suppression of miRNA activity can help elucidate the role of miRNAs in cellular processes and pathological pathways or identify and validate miRNA targets in vitro and in vivo.

All of our miRCURY LNA miRNA Inhibitors were developed with optimal LNA length, sequence and positioning and are also T_m-normalized. This ensures high uniform potency towards all miRNAs, regardless of GC content, along with excellent specificity and biological stability. As an added benefit, these inhibitors are easily taken up without the need for cholesterol conjugation. Plus, because the LNA bases are distributed throughout the entire length, the LNA inhibitor/RNA duplexes are not recognized as substrates for RNase H. This reduces off-target effects on unrelated, longer RNAs that share the same target sequence.

miRNAs are typically involved in regulating a large number of genes, so the phenotype observed due to changes in miRNA activity is actually the combined effect of deregulating several targets. Very often, a few or only just one target is the main contributor to the phenotype. Identifying this target is important to understanding miRNA function. A target site blocker (TSB) – an ASO that specifically prevents interaction of a miRNA with one of its RNA targets – allows researchers to assess the effects of a miRNA on a single target. The TSB masks the miRNA target site in the RNA target of interest, providing specific de-repression of a single intended target only, and enabling simple phenotypic interpretation.

Our miRCURY LNA Target Site Blockers are available with high purity and PK/PD properties optimized for high potency in vivo studies. LNA enhancement stabilizes the TSBs, allowing effective distribution in animal models, so you can make discoveries that might not be possible in cell culture. TSBs are also easily taken up without the need for cholesterol conjugation.