Viricidal Action of inhibition of telomerase action or inhibition of hTERT expression

Princeton Docket: 23-4002-1

Treatment options remain limited for human cytomegalovirus (HCMV), a double-stranded DNA herpesvirus with acute and chronic pathogenic effects as well as the potential to impact cancer progression. While several anti-viral drugs attenuate active infection, unmet need remains given that efficacy is limited, viral resistance is significant, and there is no existing method to permanently eradicate HCMV from the human host. As a result, once infected by HCMV, humans are infected for life and at risk of reactivation later in life as their immune competence fluctuates. HCMV seroprevalence and morbidity in immunocompromised patients and neonates infected in utero remains high in both developed and developing nations. Therefore, this virus remains a critical target for permanent effective antiviral therapy.

Princeton researchers have discovered two novel methods of telomerase (a reverse transcriptase in eukaryotic systems) inhibition that may present a novel anti-viral therapy against HCMV. Researchers have robustly demonstrated two key findings: first, infection with laboratory and clinical strains of HCMV across multiple cell lines significantly increases telomerase activity and hTERT expression; second, viral replication is sharply reduced following treatment with non-cytotoxic dose of pharmaceutical telomerase inhibitors or with treatment of an siRNA construct targeting the hTERT catalytic component of telomerase. These findings strongly support viricidal action against HCMV either through inhibition of telomerase action or indirect inhibition of telomerase via hTERT expression. In application, this technology presents a novel HCMV anti-viral treatment and a potentially more effective method to treat patients suffering from HCMV.

Applications:

Novel clinical anti-viral therapeutic for patients suffering from HCMV

Research tool to better study animal models of HCMV and other herpesviruses

Advantages:

Potential for higher efficacy compared to currently available anti-viral therapies for the treatment of HCMV given mechanism of action

Potential to be the first HCMV anti-viral therapy that eradicates HCMV from the human body

Stage of Development:

Technology has been robustly tested in vitro in Human Foreskin Fibroblast cells and Medical Research Council Cell Strain 5 cells.

Publication:

Effect of host telomerase inhibition on human cytomegalovirus - PubMed

Inventors:

Chloe Cavanaugh, Ph.D. is a student in the Princeton-Rutgers M.D.-Ph.D. program, where she is a student doctor and has completed her PhD in the Notterman Lab of the Molecular Biology Department of Princeton University. She is one of several recipients of trainee grants through the NJ ACTS program, a collaboration between Rutgers, Princeton and the New Jersey Institute of Technology that aims to spur the translation of laboratory discoveries into innovations that benefit health. Chloe received a B.S. in Neurobiology from Georgetown University.

Daniel Notterman, M.D. is a Professor in the Department of Molecular Biology at Princeton University. He is a pediatrician by clinical training having received his M.D. from New York University School of Medicine. At Princeton University, his research focuses on interactions between genetic variants and environmental signals in the developing behavioral, cognitive, and emotional phenotype of the child. His research aims to understand the interactions between specific genetic variants, environmental signals, and resulting behavioral and health outcomes. The Notterman Lab also serves as the genomics/epigenomics resource for the Future of Families and Child Wellbeing Study (FFCWS), based at The Princeton School of Public and International Affairs. 

Thomas Shenk, Ph.D. is the James A. Elkins Professor of Life Sciences in the Department of Molecular Biology at Princeton University, Emeritus. He is a virologist who has investigated gene functions and pathogenesis of adenovirus, a DNA tumor virus, and, more recently, human cytomegalovirus, a member of the herpes family of viruses.  His lab’s focus included the use of genetic and proteomic approaches for the dissection of cytomegalovirus gene functions and the cellular response to infection, as well as the development and analysis of models for study of viral latency.  Professor Shenk is a fellow of the American Academy of Microbiology and the American Academy of Arts and Sciences; and he is a member of the U.S. National Academy of Sciences and the U.S. Institute of Medicine.  He is a past president of the American Society for Virology and the American Society for Microbiology, and he served on the board of directors of Merck & Company for 11 years.  He currently serves as a member of the boards of directors of the Fox Chase Cancer Center, The Hepatitis B Foundation and Origen Therapeutics.

Maciej Nogalski, Ph.D., M.Sc., received his Ph.D. in Microbiology and Immunology at LSU Health Shreveport and his M.S. in Organic Chemistry at the University of Warsaw. He was a postdoctoral research associate and associate research scholar in the Shenk Lab. He is currently the Director of Vector Development at Ring Therapeutics.

Adam Oberstein, Ph.D. is an Assistant Professor of Microbiology and Immunology at the University of Illinois at Chicago. He completed his postdoc and Ph.D. at Princeton University and B.A. at New York University.

Intellectual Property & Development Status:

Patent protection is pending. Princeton is currently seeking commercial partners for the further development and commercialization of this opportunity.

Contact

Cortney Cavanaugh

Princeton University Tech Licensing & New Ventures • (609) 258 7256 • ccavanaugh@princeton.edu