Epstein-Barr Virus (EBV) is a herpesvirus that drives the development of a number of rare cancers, such as Burkitt’s lymphoma, nasopharyngeal carcinoma, and AIDS-related lymphoma. EBV is common and 90% of adults have faced a prior infection at some point in their lives; although EBV is usually kept under control by the immune system in healthy adults, it is dangerous to patient populations with suppressed immune systems, such as organ transplant recipients. As a result, frequent EBV testing is an essential part of post-organ transplant medical management. Identification of EBV within patient samples is quantified using EBV RNA and is used to diagnose EBV cancers. However, these EBV RNA molecules are fragile and prone to degradation, often leading to false negative readouts and poor diagnoses. Identification of novel, stable, and EBV-specific genetic markers may aid clinicians in diagnosing EBV-related cancers more easily and accurately, leading to earlier detection and more effective treatment in patients.
Description
Presented is a diagnostic tool that can accurately and rapidly identify EBV infections and EBV cancers developed using unique EBV circular RNAs, called circBARTs, which are easily extracted and measured from patient tissue samples using an accessible, low-cost, and rapid method of detection. These circBARTs were reliably detected across several types of EBV-positive tumors and were even detected in two patient samples falsely deemed to be EBV-negative through the detection of an older, more fragile EBV RNA biomarker. Increased stability of circRNAs offers a more sensitive and reliable method for EBV detection, especially in poorer quality samples. Finally, since high viral levels within EBV-infected patients are predictive for the onset of nasopharyngeal carcinoma (NPC), high expression of circBARTS could potentially be used to predict and treat the early development of EBV-related cancers.
Applications
· Effective biomarker for early diagnostic screens of EBV-related cancers
· Diagnosis of developed EBV-positive cancers
· Potential therapeutic target if shown to play a role in EBV tumorigenesis
Advantages
· Circular RNAs associated with EBV infection are stable, sensitive, and easily measured in EBV-positive tumor samples
· Detection is reliable, inexpensive, rapid, and performed using commonly available clinical laboratory equipment and reagments
Invention Readiness
In vivo data obtained
IP Status
https://patents.google.com/patent/WO2019232436A1Related Publication(s)
Toptan, T., Abere, B., Nalesnik, M. A., Swerdlow, S. H., Ranganathan, S., Lee, N., Shair, K. H., Moore, P. S., & Chang, Y. (2018). Circular DNA tumor viruses make circular RNAs. Proceedings of the National Academy of Sciences, 115(37). https://doi.org/10.1073/pnas.1811728115
