A dual-method antiviral platform for inhibiting Human Cytomegalovirus replication through host telomerase targeting

This technology treats Human Cytomegalovirus (HCMV) by inhibiting host cell telomerase, using either drugs or siRNA, which reduces viral replication and infectivity, offering a new antiviral approach that may help eliminate both active and latent infections.

Background

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.

Technology

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.

Benefits

  • Potential for higher efficacy compared to currently available anti-viral therapies for the treatment of HCMV 
  • Potential to be the first HCMV anti-viral therapy that eradicates HCMV from the human body

Applications

  • Novel clinical anti-viral therapeutic for patients suffering from HCMV 
  • Research tool to better study animal models of HCMV and other herpesviruses 

Additional info

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