Design of Novel Molecules That Regulate Telomerase

Inventor: Emmanuel Skordalakes

Tech ID: SE07001

Description: The 3-dimensional structure of the RNA-binding domain of telomerase (TRBD) was used to identify a novel target binding site involved in stabilizing and regulating the activity of telomerase by researchers at The Wistar Institute. Telomerase is a specialized DNA polymerase that is responsible for preserve the integrity of linear chromosomes during mitosis by adding multiple short protective, oligonucleotide repeats (telomeres) to their ends. There is now clear evidence that links the telomerase enzyme to both cancer and aging. For example 90% of human tumors show high levels of activity of this enzyme while it is dormant in adjacent somatic cells.

The telomerase molecule is a complex between a protein component (an enzyme that is responsible for adding the repeats) and an RNA component (that serves as a template for the repeats). A stable ribonucleoprotein complex is essential for the activity of the enzyme. However, until recently it has not been clear how the enzyme interacts with the RNA template. Wistar researchers have identified a nucleic acid binding site in the protein component of telomerase that is capable of accommodating both single- and double-stranded RNA. It includes several motifs that have previously been implicated, by biochemical and mutagenesis studies, in RNA binding. Small molecule compounds that target this site can act as inhibitors or as activators of telomerase, effectively modifying cell proliferation and turnover. 

Key Words: telomerase, senescence, cancer therapy, rational drug design

Applications and Advantages: This technology provides a method for designing and screening drugs that target the RNA binding site of telomerase. Modifiers of telomerase that act at the TRBD domain could be developed using in silico and/or in vitro methods. Telomerase activators could be useful in treating diseases associated with senescence, such as aging, or in promoting tissue regeneration, while telomerase inhibitors could be novel therapies for a range of cancers.

Intellectual Property Status: This technology is protected by a provisional patent application.

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.

Contact:

Meryle J. Melnicoff
Director, Business Development
The Wistar Institute
3601 Spruce Street
Room 322
Philadelphia, PA 19104
Phone: (215) 898-0049
Fax: (215) ) 495-6861
melnicoff@wistar.org

Last Updated: Jan-08