A Copenhagen-based, Danish team from the drug firm Santaris Pharma conducted promising experiments on African green monkeys, involving the blocking of microRNA activity in the non-human primates.
MicroRNAs bind to messenger RNAs and regulate protein synthesis by silencing gene expression. This process has been implicated in a number of disorders including cancer and cardiovascular disease.
In 2005, studies had been undertaken to detect specific micro RNAs in zebrafish embryos using synthetic RNA analogues, locked nucleic acids (LNAs) or LNA-antimiR compounds. These enable an increase in the effectiveness of the binding of DNA molecules to complementary RNA sequences. Following success, LNA proved that it was efficient for use in microRNA research.
In 2006, the scientists injected drugs containing LNA-based compounds into the monkeys. The testing targeted microRNA-122, which is expressed in the liver and also evidenced to assist the replication of hepatitis C virus in liver cells. It was also known that the activity of microRNA-122 could be easily monitored in animals.
Earlier studies on mice indicated that the inhibition of microRNA-122, resulted in lower cholesterol levels as well as blocking of the replication of hepatitis C virus.
Administration of three doses of 10 mg kg-1 LNA-antimiR to the monkeys, over five days resulted in a decrease of 30% in the total plasma cholesterol. This lasted for three weeks; proving a longer lasting effect in comparison to the mice. There was no sign of LNA-associated toxic effects in the liver or kidneys of the animals.
These experiments on non-human primates are the first in the field to demonstrate the silencing of microRNAs. The results have demonstrated the utility of LNA and lead to possibilities for targeting disease-associated microRNAs and mRNAs, and ultimately to the investigation of biological pathways and therapeutic targets. These may result in breakthroughs in various types of cancer, cardiac diseases and metabolic problems.
Nevertheless, the permanent implications are still unclear and thus, extensive research needs to be continued. It may even assist in developing a treatment for the diseases, if not a cure.
Elmee Huda
42037305
References:
http://news.bbc.co.uk/2/hi/health/7314676.stm
http://www.nature.com/nature/journal/v452/n7189/full/7189xa.html
