High Lead Expression of Soluble CMV UL97 and Development of an Assay to Screen Inhibitors

Summary The Coen Lab has expressed UL97 and UL97 fusion proteins and developed an assay to identify agents that inhibit or activate UL97 to be used in the treatment of human cytomegalovirus (HCMV) infection.

HCMV is a beta herpes virus that causes significant pathology in individuals who are immunosuppressed (cancer patients, HIV patients, transplant patients) and in children born with primary HCMV infection. UL97 is a HCMV gene which encodes a protein kinase. UL97 kinase can phosphorylate nucleoside analogs such as the antiviral drugs acyclovir and ganciclovir as well as exogenous protein and peptide substrates. Although the role of UL97 is still under investigation, recent studies showed that UL44, a protein essential for HCMV DNA replication is a natural substrate of UL97.

Harvard's intellectual property portfolio includes the following patent: US 5,914,244 issued June 22, 1999.

Applications The use of currently approved drugs to treat HCMV infections (Ganciclovir, Foscarnet, cidofovir) is limited by their acute- and long term toxicity (reproductive toxicity, carcinogenicity). Moreover, these drugs share a common mechanism of action, targeting viral DNA polymerase, which makes cross-resistance a potential problem. This assay could be used to discover new drugs against human cytomegalovirus. Targeting UL97, these new drugs offer a valuable alternative against drug-resistant strains.

Inventor(s): Coen, Donald M.

Type of Offer: Licensing



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