News | June 6, 2000

Ribozyme Pharmaceuticals Going Into Clinical Trials with Herzyme, Ribozyme Directed Against HER-2

Ribozyme Pharmaceuticals Going Into Clinical Trials with Herzyme, Ribozyme Directed Against HER-2
Scientists from Ribozyme Pharmaceuticals Inc. (Boulder, CO) reported at the annual RNA Society Meeting in Madison on a new and proprietary ribozyme motif that has enhanced nuclease resistance, while maintaining optimum activity. This new motif was used to generate Herzyme, RPI's lead compound targeted directed against the HER-2 gene for treatment of breast and ovarian cancer. Herzyme is in pre-clinical studies at Medizyme Pharmaceuticals, RPI's joint venture with an affiliate of Elan Corp.

Ribozymes, which are naturally occurring catalytic RNAs, can also be designed and chemically synthesized to inhibit the production of proteins through the specific cleavage of the disease-causing mRNA. Recently, RPI showed that proprietary chemical modifications create ribozymes that are stable and active in human serum for several days.

This new motif, dubbed Zinzyme, was isolated by screening a library of modified molecules—some 1014 large—for those species that retained optimum activity. Previously, ribozymes modified for ribonuclease stability had significantly decreased activity. The first ribozyme in this series, Amberzyme, was described earlier this year (reference 1).

These new nuclease-resistant ribozyme motifs add to RPI's ribozyme arsenal by providing the ability to cleave previously inaccessible sites on target mRNA, allowing for rapid design of ribozymes against an extended range of drug targets.

In his presentation "A Novel Ribozyme Identified by In Vitro Selection Demonstrates Efficacy in Breast Cancer Cell Line," first author Shawn Zinnen reported that treatment with Zinzyme resulted in significant inhibition of cell proliferation of a breast cancer cell line as compared to controls. The ribozyme mechanism of action was confirmed by PCR analysis in which intracellular levels of HER-2 mRNA were significantly reduced.

"The importance of this new motif has already been demonstrated in its activity against HER-2," said Nassim Usman, senior vice president of research. "We look forward to exploring this new generation of ribozymes for future therapeutics."

RPI is a leader in ribozyme therapeutic development. RPI is partnered with Eli Lilly for development of an anti-Hepatitis C virus ribozyme already in clinical trials designed to study safety and to assess the effect of the compound on HCV viral RNA levels in chronic Hepatitis patients. RPI is partnered with Chiron Corporation for the development and commercialization of Angiozyme, an anti-angiogenic ribozyme designed to inhibit the growth of new blood supplies to tumors and thus prevent tumor growth and metastasis. Angiozyme is in Phase I/II clinical trials in cancer patients at the Cleveland Clinic.


  1. Beaudry et al., "In vitro selection of a novel nuclease-resistant RNA phosphodiesterase," Chemistry & Biology, 7:323-334, 2000.

For more information: Ribozyme Pharmaceuticals Inc., 2950 Wilderness Place, Boulder, CO 80301. Tel: 303-449-6500. Fax: 303-449-6995.

Edited by Laura DeFrancesco