Isis Pharmaceuticals and Rosetta Genomics Announce Joint Research Collaboration to Develop Micro-RNA Related Therapies for the Treatment of Liver Cancer

Research Published in Cell Metabolism Demonstrates Therapeutic Potential of

MicroRNA as a Drug Target Using Antisense

Feb 22, 2006, 00:00 ET from Rosetta Genomics Ltd.

    CARLSBAD, Calif. and REHOVOT, Israel, Feb. 22 /PRNewswire/ -- Isis
 Pharmaceuticals, Inc. (Nasdaq:   ISIS) and Rosetta Genomics Ltd., a privately
 held biopharmaceutical company that is developing microRNA-based diagnostic
 and therapeutic products, today 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
 (HCC). The collaboration will bring together the complementary expertise of
 both companies in miRNA and leverage Rosetta's database of novel miRNA genes
 and Isis' expertise in oligonucleotide chemistry and antisense drug discovery
 and development.
     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 recently conducted
 by Isis 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 C. Frank Bennett,
 Ph.D., Senior Vice President, Antisense Research at Isis. "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 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.
     "MiRNAs appear to regulate at least one-third of all gene expression and
 represent a new class of drug targets for the pharmaceutical industry," said
 Amir Avniel, President of Rosetta Genomics. "We are pleased to join forces
 with Isis and view antisense as the optimal platform for inhibiting miRNA
 function. Given the prevalence of HCC and the limited treatment options for
 patients with hepatocellular carcinoma, we are especially eager to begin
 working with Isis to discover and develop potential new treatment options for
 patients around the world."
     ABOUT MicroRNA (miRNA)
     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.
     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% of people with liver cancer die within five-years
 of diagnosis.
     Rosetta Genomics Ltd., a private biopharmaceutical company with operations
 in the United States and Israel, is a world leader in the development of
 microRNA-based therapeutic and diagnostic agents. The company has developed a
 large and growing database of novel microRNA genes identified via its
 proprietary chip technology and computational algorithms. The company has
 filed several patents related to its novel microRNAs. Rosetta's current
 development endeavors include unique classes of microRNA agents with potential
 applications in the diagnosis and treatment of a wide range of diseases. For
 more information, please visit Rosetta Genomics at:
     Isis is exploiting its expertise in RNA to discover and develop novel
 drugs for its product pipeline and for its partners. The Company has
 successfully commercialized the world's first antisense drug and has 11
 antisense drugs in development to treat metabolic, cardiovascular, ocular and
 inflammatory diseases, and cancer. In its Ibis division, Isis is developing
 and commercializing the TIGER biosensor system, a revolutionary system to
 identify infectious organisms. As an innovator in RNA-based drug discovery and
 development, Isis is the owner or exclusive licensee of approximately 1,500
 issued patents worldwide. Additional information about Isis is available at
     This press release includes forward-looking statements regarding the
 research collaboration agreement between Isis and Rosetta Genomics to discover
 and develop antisense drugs that regulate miRNAs for the treatment of
 hepatocellular carcinoma. Any statement describing Isis' goals, expectations,
 intentions or beliefs is a forward-looking statement and should be considered
 an at-risk statement, including those statements that are described as Isis'
 goals. Such statements are subject to certain risks and uncertainties,
 particularly those inherent in the process of discovering, developing, and
 commercializing drugs that are safe and effective for use as human
 therapeutics, and in the endeavor of building a business around such products.
 Isis' forward-looking statements also involve assumptions that, if they never
 materialize or prove correct, could cause its results to differ materially
 from those expressed or implied by such forward-looking statements. Although
 Isis' forward-looking statements reflect the good faith judgment of its
 management, these statements are based only on facts and factors currently
 known by Isis. As a result, you are cautioned not to rely on these
 forward-looking statements. These and other risks concerning Isis' programs
 are described in additional detail in Isis' annual report on Form 10-K for the
 year ended December 31, 2004, and its quarterly report on Form 10-Q for the
 quarter ended September 30, 2005, which are on file with the SEC. Copies of
 these and other documents are available from the Company.

SOURCE Rosetta Genomics Ltd.