Methods and compositions for inhibiting herpesviral replication

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...

Reexamination Certificate

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C435S006120, C435S007100

Reexamination Certificate

active

10885862

ABSTRACT:
This invention provides methods of screening for compounds that inhibit herpesviral transcription and replication. The methods comprise screening test compounds for ability to enhance the activity of homeodomain transcription factor PDX1 in repressing transcription of herpesviral genes (e.g., the IE gene of cytomegalovirus). Transcriptional repression by PDX1 can be monitored using an expression vector comprising a reporter gene operably linked to a PDX1-binding, upstream transcription regulatory sequence of the herpesvirus. The invention further provides methods and pharmaceutical compositions for stimulating PDX1-mediated transcriptional repression in a subject and for treating diseases and conditions associated with herpesviral infection.

REFERENCES:
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Lundquist et al. A Strong Negative Transcriptional Regulatory Region between the Human Cytomegalovirus UL127 Gene and the Major Immediate-Early Enhancer. Journal of Virology, Nov. 1999, vol. 73, No. 11, pp. 9039-9053.
Isomura et al. The Human Cytomegalovirus Major Immediate-Early Enhancer Determines the Efficiency of Immediate-Early Gene Transcription and Viral Replication In Permissive Cells at Low Multiplicity of Infection. Journal of Virology, Mar. 2003, vol. 77, No. 6, pp. 3602-3614.
Macias et al. Cellular or Viral Protein Binding to a Cytomegalovirus Promoter Transcription Initiation Site: Effects on Transcription. Journal of Virology, Jun. 1996, vol. 70, No. 6, pp. 3628-3635.
Lashmit et al. Cellular Repressor Inhibits Human Cytomegalovirus Transcription from the UL127 Promoter. Journal of Virology, May 2004, pp. 5113-5123.
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