The latest technology termed microRNA (miRNA) promises to regulate gene expression to cut cholesterol levels. This technique has also been used to stop hepatitis C infecting cells.
This cutting edge technology is related to earlier forms of RNA interference, unlike its counterparts it works by inhibiting the increases in the amount of protein that is produced by intercepting the molecules. In essence it acts as a ‘brake’ on the mRNA translation.
41442621
This cutting edge technology is related to earlier forms of RNA interference, unlike its counterparts it works by inhibiting the increases in the amount of protein that is produced by intercepting the molecules. In essence it acts as a ‘brake’ on the mRNA translation.
MicroRNA’s are thought to control up to 30 percent of all gene activity, directing and expressing a whole network of genes rather than just single genes. These therapies have failed thus far as it is difficult to get the therapeutic molecule into the target cell. Work conducted at Santaris Pharma in Hørsholm, Denmark, however has lead to the absorption of the miRNA through an inhibiting drug. This eliminates the need for a “delivery vehicle”. The company has been targeting a miRNA called miR-122, which is thought to regulate up to 450 genes, around 100 of which are involved in cholesterol and lipid metabolism. It is only expressed in liver cells.
This miRNA inhibitor, or antimiR, was readily taken up by liver cells (in mice) and lowered cholesterol by up to 35 per cent. The more antimiR that was given, the greater the cholesterol-lowering affect it had on the mice. Inhibiting miR-122 also seems to protect the liver against hepatitis C infection; this is suggested by the culture tests. Without miRNA-122 viral replication is no longer supported and therefore antimiR-122 has the potential for hepatitis C and cholesterol reduction.
miRNA find it easier to cross cell membranes as they are single stranded and shorter than other RNA therapies. The nucleotide structure of antimiR has also been modified to make it more stable. It now last longer in the body and ensures stronger bonding to miRNA. This makes the treatment much more effective.
Although some researches question the wisdom of developing miRNA inhibitors before understanding the miRNA regulatory system, most agree that the results do seem promising. "People have been trying to knock down miRNA since it was first discovered," says Graham Brock, director of target and drug discovery at Ordway Research Institute in Albany, New York. "It has been done in cell lines and animal models, but I think this is the first time it has been done therapeutically."
Speculation has also been made in the use of miRNA to down-regulate cancer. Further screening of molecules is now in the process.
This miRNA inhibitor, or antimiR, was readily taken up by liver cells (in mice) and lowered cholesterol by up to 35 per cent. The more antimiR that was given, the greater the cholesterol-lowering affect it had on the mice. Inhibiting miR-122 also seems to protect the liver against hepatitis C infection; this is suggested by the culture tests. Without miRNA-122 viral replication is no longer supported and therefore antimiR-122 has the potential for hepatitis C and cholesterol reduction.
miRNA find it easier to cross cell membranes as they are single stranded and shorter than other RNA therapies. The nucleotide structure of antimiR has also been modified to make it more stable. It now last longer in the body and ensures stronger bonding to miRNA. This makes the treatment much more effective.
Although some researches question the wisdom of developing miRNA inhibitors before understanding the miRNA regulatory system, most agree that the results do seem promising. "People have been trying to knock down miRNA since it was first discovered," says Graham Brock, director of target and drug discovery at Ordway Research Institute in Albany, New York. "It has been done in cell lines and animal models, but I think this is the first time it has been done therapeutically."
Speculation has also been made in the use of miRNA to down-regulate cancer. Further screening of molecules is now in the process.
Amy Beugelsdyk
41442621
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