Ryan Flynn

E-mail: flynn214@umn.edu

Year entered: 2008

Thesis Advisor: Nicola Philpott

Degrees received:
B.A., Austin College, Sherman, TX

Thesis research:

The use of lentiviral vectors as a delivery system for genetic material has great potential for gene therapy. However, integration of a viral genome into host chromosomes can cause cancer mutagenesis. To avoid this problem, we have developed non-integrating lentiviral vectors (NILVs) that are effective at delivering genes to non-mitotic cells for long periods of time. In the absence of integration the effectiveness of NILVs in mitotic cells is limited and for this reason the use of NILVs for cancer therapy has been overlooked. Epstein-Barr virus (EBV) infects an overwhelming majority of the population and can lead to severe cancer malignancies such as Hodgkin’s disease, Burkitt’s lymphoma, post-transplant lymphoproliferative disorder and nasopharyngeal carcinoma. All EBV-associated malignancies express EBV nuclear antigen 1 (EBNA1) during latency. EBNA1 ensures maintenance of EBV by tethering the EBV genome to host chromosomes via its interaction with the EBV Family of Repeats (FR) motif. The goal of our project is to maintain viral vector genetic information within dividing cells by usurping the EBNA1 interaction with the EBV FR. We have generated several NILVs that contain the herpes simplex virus 1 Thymidine Kinase (TK) suicide gene. These NILVs are currently being used to determine whether EBNA1-expressing cells can be specifically killed upon administration of the pro-drug, Ganciclovir. Results from this project have the potential to lead to the creation of a new, non-toxic cancer therapy by taking advantage of EBNA1-expression in EBV malignancies.