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Design of Novel Molecules That Regulate Telomerase

Tech ID

We used the 3-dimensional structure of the catalytic subunit of telomerase to identify novel target binding sites essential for telomerase ribonucleoprotein assembly and activity. Telomerase adds multiple identical repeats of DNA (telomeres) to the 3’-end of eukaryotic chromosomes thus providing the genomic stability required for cell survival. There is now clear evidence that links telomerase to both cancer and aging. For example 90% of human cancers show high levels of activity of this enzyme when such activity is absent in most healthy tissues. The absence of telomerase activity (in adults) in healthy tissues leads to loss of ~50-100 bases of telomeric DNA with every cell division. When telomeres reach a critically short length, cells enter a permanent state of dormancy to prevent genomic instability, a process known as senescence, the hallmark of aging. Our goal is to identify compounds that regulate telomerase function that can be used to combat cancer and age related diseases.

Key Words
aging, Cancer, drug design, telomerase
Applications and Advantages

This technology provides a method for designing and screening drugs that target the catalytic subunit of telomerase. Modulators of telomerase activity could be developed using in silico and/or in vitro methods. Telomerase activators could be useful in treating age related diseases, while telomerase inhibitors could be novel therapies for a range of cancers.

Intellectual Property Status

PCT Application No. PCT/US2008/080604 (WO 2009/055364, published 04/30/2009); U.S. Patent Application No. 12/701,843 (US-2010-0160260, published 06/24/2010); U.S. Patent Application No. 12/701,947 (US-2010-0158798, published 06/24/2010); U.S. and international applications have been filed.

Licensing Opportunity

Wistar is seeking to collaborate with a corporate partner to use this technology to develop small molecule modulators of telomerase. An exclusive license or sponsored research to further develop the technology would be considered.

Relevant Publication(s)

Andrew J. Gillis, Anthony, P. Schuller & Emmanuel Skordalakes, Structure of the Tribolium castaneum telomerase catalytic subunit TERT, Nature 455:633-637, 2008.

Rouda S, Skordales E. Structure, 2007, Nov. 15(11):1403-12. Structure of the RNA binding domain of telomerase: Implications for RNA recognition and binding.