Novelty: Luciferase-tagged CMV strains for rapid sensitive anti-CMV drug screening.
Value Proposition: To date, the identification of anti-viral agents for cytomegalovirus (CMV), a major threat in immunocompromised people and congenitally-infected children, relies on evaluation of viral replication via plaque assays and real-time PCR. However, these assays are laborious, time-consuming and often not conclusive. New drug screening methods, such as the one described below, are urgently needed. This new technology provides CMV strains expressing luciferase under control of the CMV-DNA polymerase (POL) or the true late pp28 promoter, applicable for the high-throughput screening of novel anti-CMV therapeutics. Advantages include:
• Rapid, sensitive, easy-to-use, low-cost identification of anti-viral drugs via luciferase-reporter assay
• Reliable quantitative evaluation of drug efficiency and assessment of drug inhibitory mechanism
• Applicable for high-throughput drug screening
Technical Details: Johns Hopkins researchers have engineered recombinant CMV strains expressing luciferase under the control of the POL or the true late pp28 promoter, useful as a robust new reporter assay to determine CMV inhibition by anti-viral agents. There is still a great demand for novel therapeutics for CMV, a life-threatening infection for people with weakened immune system such as organ transplant recipients or new-born infants, due to the frequent emergence of resistant viral strains and severe side-effects of existing drugs. However, current drug screening using plaque assays and real-time PCR is inefficient and often inaccurate. Therefore, this technology presents a novel screening tool for anti-CMV compounds using luciferase-tagged CMV strains, enabling the simple and highly precise monitoring and quantification of viral replication. Late CMV protein expression highly correlates with the production of infectious progeny. Hence, the here-presented pp28-luciferase CMV strain allows screening for compounds that target steps prior to or during DNA replication. Moreover, a recombinant CMV strain expressing luciferase under control of the early POL promoter is provided, therefore presenting a useful system to compare structurally related compounds and gain mechanistic insights into their mode of action. Together, the ease of use, low cost, and high sensitivity make this luciferase reporter system an attractive new tool for the rapid and accurate high-throughput screening of novel anti-CMV compounds.
Looking for Partners: To develop and commercialize the technology as a robust screening tool for anti-CMV agents.
Publications/Associated Cases: Virol J. 2011 Jan 26;8:40.
