Isis, Rosetta Genomics to collaborate on microRNA-related liver cancer therapies

By Elaine Rigoli

Tampa, Fla., Feb. 22 -Isis Pharmaceuticals, Inc. and Rosetta Genomics Ltd. announced a joint research collaboration to discover and develop antisense drugs that regulate microRNAs (miRNAs) for the treatment of the most prevalent type of liver cancer, hepatocellular carcinoma.

This partnership will leverage Rosetta's database of novel miRNA genes and Isis' expertise in oligonucleotide chemistry and antisense drug discovery and development, according to a company news release.

Recent Isis research shows 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, the release stated.

Antisense drugs bind to complementary RNA sequences, such as miRNAs, inhibiting the function of miRNAs.

"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 C. Frank Bennett, PhD, Isis senior vice president of antisense research, in a statement.

"Our recently published research demonstrates pharmacological activity in vivo using well validated antisense chemistry to inhibit miRNAs. We believe our collaborative efforts with Rosetta Genomics will enable both companies to take advantage of miRNAs as potential new drug targets for the treatment of a range of diseases, including liver cancer."

Isis published research in the February 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, the release said.

Worldwide, hepatocellular carcinoma 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% of people with liver cancer die within five years of diagnosis.

Rosetta Genomics, a private biopharmaceutical company with operations in the United States and Rehovot, Israel, develops microRNA-based therapeutic and diagnostic agents.

Based in Carlsbad, Calif., Isis is exploiting its expertise in RNA to discover and develop drugs for its product pipeline and for its partners.

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