RNA blocker to combat diseases
doi:10.1038/nindia.2010.157 Published online 10 November 2010
Researchers have found a new way to block the activity of microRNA (miRNA), a tiny type of RNA that suppresses the expression of certain genes and proteins. This tiny RNA is present in every type of cell, and has been linked to various conditions such as cancer, schizophrenia, cardiovascular disease and renal function disorders.
This new method of blocking miRNA may open up new avenues for battling a host of diseases. To disrupt the activity of miRNA, the researchers used modified antagomirzymes, known as DNAzymes.
They modified the DNAzymes using locked nucleic acid (LNA), a nucleic acid analogue that displays unprecedented hybridization affinity towards DNA and RNA molecules. The researchers designed DNAzymes for two different sites of miRNA that were present both within the precursor and the mature form of miRNA. The cleavage and functional activities of these DNAzymes were shown to be comparable to those of their LNA-modified counterparts in lab studies.
The study showed that the cleavage efficiency of LNA-modified DNAzymes is five times higher than that of unmodified DNAzymes. This enhancement is due to an LNA-mediated improvement in the hybridization between the DNAzymes and the target miRNA complex.
A direct quantitative estimate of miRNA cleavage showed that LNA-modified DNAzymes effectively down-regulate the levels of mature miRNA (up to 50%) over the corresponding unmodified DNAzymes. The researchers say that these results provide formative evidence of the successful employment of LNA-based DNAzymes against miRNA.
- Kaur, H. et al. "Locked onto the target”: Increasing the efficiency of antagomirzymes using locked nucleic acid modifications. Biochemistry 49, 9449-9456 (2010) | Article