The Technology:

Glioma is an aggressive cancer with a median survival of less than 12 months from diagnosis. Because of their location in the brain, most gliomas can not be fully removed by surgical resection. Recognizing that traditional small molecule therapeutics have not provided effective treatments for glioma, and that matrix metalloproteinase expression is correlated with tumor invasion and metastasis, researchers at the University of Tennessee Health Science Center have demonstrated that blocking matrix metalloproteinase (MMP) expression with DNAzymes is able to inhibit tumor growth. In animal studies, a single intracranial injection of an anti-MMP-9 DNAzyme reduced glioma size by 60%. In similar experiments investigating the ability of MMP-9 inhibition to impact breast cancer, weekly administration resulted in a 70% reduction in the size of mammary tumors. The investigators are currently exploring the role of MMP-9 inhibition in melanoma and metastasis.

Unlike traditional small molecules which inhibit matrix metalloproteinases by binding to the active site of the enzyme, catalytic DNAzymes work by degrading the mRNA and blocking the protein from being produced. In both in vitro and in vivo models the inventors demonstrated that DNAzymes targeting MMP-9 are taken up by cells and inhibit production of the target enzymes.

Benefits:

• No existing effective chemotherapeutic agents for the treatment of glioma.

• Increased safety – DNAzymes are extremely targeted and will only degrade the mRNA of interest, reducing treatment side effects.

The Inventor:

Dr. Tayebeh Pourmotabbed is a Professor of Molecular Sciences in the College of Medicine at the University of Tennessee Health Science Center. Her research interests include cancer therapy, understanding the structure-function relationship of matrix metalloproteinases, and identifying risk factors in Alzheimer’s and coronary artery disease.

Patents:

• One issued US patent (US 12/390,628)

Reference: PD-03021