Table 3.
MiRNA-targeted CLL therapies
| Therapy | Comments |
|---|---|
| Mimic miRNA | A mimic miRNA represents a partially double-stranded RNA that mimics endogenous precursor miRNA and is processed to form the active miRNA molecule that targets specific mRNAs. |
| Antagomir | An antagomir is a single-stranded 23-nt RNA molecule complementary to the targeted miRNA that has been modified to increase the stability of the RNA and protect it against degradation by a partial phosphorothioate backbone in addition to 2′-O-methoxyethyl. miRNA/antagomir duplexes induce degradation of the miRNA and recycling of the antagomir.89 |
| Anti-miRNA oligonucleotide | An anti-miRNA oligonucleotide is a single-stranded, chemically modified (usually with a 2′-O-methyl group) 17- to 22-nt nucleic acid molecule that is directed against a specific miRNA. It functions as an ASO via Watson-Crick binding pairs with the miRNA of interest.90 |
| Locked nucleic acid (LNA) | A LNA is an ASO modified using LNA technology, and LNA anti-miRNAs have the same mechanism of action that ASOs/anti-miRNA oligonucleotides do but with the advantages of increased stability and strength of target binding.91 |
RNA inhibition can be used to treat CLL in different ways: directly targeting miRNAs that participate in CLL initiation and progression and using miRNA molecules as therapeutic agents against mRNA in genes involved in CLL. The miRNAs and anti-miRNA agents are still in preclinical studies, and in vitro toxicity studies are underway.
ASO indicates antisense oligonucleotide.