Small Molecule Targeting of Viral Non-Coding RNA EBER1 to Detect and Treat Latent EBV

SummaryThe goal of this SBIR program is to develop novel small molecule probes and inhibitors targeting a viral non coding RNA expressed at high levels in all forms of Epstein Barr VirusEBVtumorsEBERis a highly conservedviral encoded small nuclear RNA expressed consistently at high levels in all EBV tumorsEBERis required for EBV tumorigenesis in mouse models and functionally interacts with ribosomal subunit Lthat has been implicated in the telomerase immortalization and TLR signaling pathwaysThe project addresses an unmet medical need to detect and treat EBVassociated cancers and related diseasesEBV latent infection is a causal factor in undifferentiated nasopharyngeal carcinomaendemic Burkitt s lymphomaof Hodgkin s lymphomasof non Hodgkin s lymphomasNK T cell lymphomaof gastric carcinomasand the majority of post transplant lymphoproliferative diseaseEBV primary infection is the major cause of infectious mononucleosisEBV infection is also implicated as a causal agent of multiple sclerosisTo dateno viral specific therapeutic exists for treatment of EBV latent infectionnor are there non invasive methods to detect EBV latent infection in tumorsEBERis among the most abundant and stable nuclear non coding RNAs expressed exclusively in EBV positive tumors and therefore represents an ideal target for detection and treatment of EBV specific tumorsWe propose to develop novel and safe small molecules that can selectively bind EBERand inhibit its interaction with LThe product that ultimately results from this proposal is a small molecule probe that selectively binds EBERRNAand can be further developed for the detection and treatment of EBV malignancies and associated diseases Project NarrativeThe goal of the SBIR proposal is to develop novel small molecule probe and drug candidate for the detection and treatment of Epstein Barr VirusEBVlatent infectionEBV latency is associated with subtypes of carcinomas and lymphomasas well as autoimmune diseaseincluding multiple sclerosisEBV latent infection can only be detected through late stage biopsy and molecular analysisWe propose to target a viral non coding RNAEBERexpressed at high levels in all EBV tumors and latent infectionscontributing to viral inflammatory responsesand thereforean attractive target for small molecule probe detection and therapeutic intervention