miRCURY LNA miRNA Family Power Inhibitors are specifically designed to silence entire families of miRNAs, rather than individual family members. Through careful design, we have developed special family inhibitors that knock down all family members, while retaining specificity for the targeted family (see figure Example of miRNA family inhibitor design
). This is achieved through the following design criteria:
- Sequence optimization: identification of a target sequence sufficiently short to be shared by family members and sufficiently long to define the family.
- Mixed-base synthesis: when target sequences differ at a single position, we use a mixture of two bases at the corresponding position during the synthesis of the antisense oligonucleotide. This allows us to generate two oligonucleotides in a single oligonucleotide synthesis reaction.
- Mixture of inhibitors: when it is not possible to target a whole family using a single nucleotide synthesis, we provide a mixture of two or more inhibitors that make up the family inhibitor.
- LNA optimization: family inhibitors are short 10–16mers, but enhanced LNA content ensures that they all have the same target affinity (Tm) as our individual miRCURY LNA miRNA inhibitors.
The miRCURY miRNA Family Power Inhibitors have phosphorothioate backbones for enhanced stability and potency. All 43 Family Power Inhibitors are also available in a library plate format (miRCURY LNA miRNA Inhibitor Libraries).
We have developed inhibitors for more than 40 human miRNA families that are conserved in mouse. miRCURY LNA miRNA Family Power Inhibitors have been designed only for miRNA families in which the design criteria described above provide an advantage over simply using a mixture of individual inhibitors of all miRNA family members.
We define miRNA families as highly related miRNAs that share an identical seed sequence (nucleotides 2–8). This is particularly important for target recognition, although the miR-200 family is one of the few exceptions to this rule.
Some very large, miRBase-defined miRNA families, such as the hsa-miR-506, hsa-miR-515 and hsa-miR-548 families, comprise miRNAs with similar sequences but with different seed sequences. These families are not represented in our miRCURY LNA miRNA Family Power Inhibitors.
Power Inhibitors are not recommended for use with cells or cell lines derived from muscle or the central nervous system (CNS). These cell types are known to be particularly sensitive to sequence-dependent toxicity of phosphorothioate-modified oligonucleotides.