Isis and Rosettta form microRNA therapy deal
research collaboration to develop microRNA related therapies for
the treatment of liver cancer, demonstrating the therapeutic
potential of microRNA as a drug target using antisense.
MicroRNAs are naturally expressed small RNAs that play a critical role in many essential cellular functions in the body, including protein production, cell differentiation and cell death; abnormalities in miRNA function may play a role in human disease.
Antisense drugs bind to complementary RNA sequences, such as miRNAs, inhibiting the function of miRNAs. Research has shown that antisense inhibition is a powerful technique to regulate the function of miRNAs, which are naturally expressed small RNAs believed to play a central role in the progression of many forms of cancer and other serious illnesses.
"We believe miRNAs are most easily accessible using antisense technologies and look forward to working with Rosetta Genomics to discover antisense drugs targeted to miRNAs for the treatment of liver cancer," said Frank Bennett, senior vice president, Antisense Research at Isis.
MiRNA molecules are a recently discovered class of small RNA molecules that occur naturally within all mammalian cells and are critical in cell function in humans, animals, and plants.
There are at least 330 confirmed miRNA genes in the human genome and there are many other predicted miRNAs remain yet to be confirmed.
MiRNAs are believed to regulate at least one-third of genes in the human genome and are also likely play significant roles in the manifestation of many disease states, including cancer and many metabolic and infectious diseases.
Isis recently published new research in the February 2006 issue of Cell Metabolism demonstrating that antisense inhibition is a powerful technique in regulating the function of miRNAs in the liver.
To determine the role of miR-122 in the adult liver, Isis scientists inhibited miR-122 with an antisense oligonucleotide in mice.
The antisense inhibition of miR-122 in normal and high fat-fed mice resulted in a significant improvement in numerous metabolic and cardiovascular risk factors as evidenced by reduced plasma cholesterol levels, increased hepatic fatty-acid oxidation, decreased hepatic fatty-acid and cholesterol synthesis rates and reduced fat in the liver (steatosis).
These results implicate miR-122 as a key regulator of cholesterol and fatty-acid metabolism in the adult liver and suggest that miR-122 may be an attractive therapeutic target for cardiovascular and metabolic diseases.
Hepatocellular carcinoma is the most common primary cancer of the liver. Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths in men and the seventh most common in women, according to the National Cancer Institute.
A recent study published in the New England Journal of Medicine found that 95 per cent of people with liver cancer die within five-years of diagnosis.