Intervention in and Prevention of Epstein-Barr Virus Infection through Targeting of the EBNA2/CBF1 Interaction

Peptides having substantial homology with a cellular DNA-binding domain (known as CBF1/RBPJk) of the Epstein-Barr virus EBNA2 protein are the subject of this invention. EBV EBNA2 protein is one of the first viral proteins expressed after EBV infection. EBNA2 is a transcriptional activator that regulates viral latency gene expression and activates expression of cellular genes. EBNA2 is critical for the establishment of a latent infection in the B cell, and ultimately can lead to tumorigenesis. EBNA2 does not bind directly to DNA but rather targets promoters through interaction with a cellular DNA-binding protein CBF1. Thus these peptides compete with the native EBV EBNA2 protein for interaction with CBF1. EBV DNA and latent gene expression are found in a variety of malignancies such as Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkins lymphoma, post-transplant lymphoma, primary central nervous system lymphoma in AIDS, systemic B cell lymphomas in the immunocompromised, nasal T cell lymphomas and a subset of gastric carcinomas. Pharmaceutical compositions containing claimed peptides are useful in protecting against EBV-related lymphoma development. Description (Set) Proposed Use (Set) Small peptide therapeutics prevent critical interaction between EBV viral protein and cellular protein. These therapeutics are particularly useful for immunosuppressed individuals, such as organ transplant patients and viral (HIV) or cancer (lymphoma, nasopharyngeal carcinoma)-related diseases.
Patent (Set) 6,162,440; 6,495,144;

Patents:
US 6,162,440

Inventor(s): Hayward, S.Diane

Type of Offer: Licensing



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