title: Targeted disruption of EBNA1 in EBV-infected cells attenuated cell growth.
abstract: Epstein Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) plays a pivotal in an EBV episome replication and persistence. Despite considerable attempts, there are no EBV drugs or vaccines. We attempted to eradicate EBV episomes by targeting EBNA1 using the transcription activator-like effector nucleases (TALEN) (E1TN). E1TN-mediated transient knockout (KO) of EBNA1 reduced EBNA1 expression, and caused significant loss of EBV genomes and progressive death of EBV-infected cells. Furthermore, when a mixture of EBV-infected Burkitt's lymphoma (BL) cells and EBV-negative BL cells was targeted by E1TN, EBV-negative cells were counter-selected while most EBV-infected cells died, further substantiating that EBNA1 KO caused selective death of EBV-infected cells. TALEN-mediated transient targeting of EBNA1 attenuated the growth of EBV-infected cells, implicating a possible therapeutic application of E1TN for EBV-associated disorders. [BMB Reports 2016; 49(4): 226-231].
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul 06351, Korea.
authors.forename: Ka-Won
authors.initials: KW
authors.lastname: Noh
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul 06351, Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University; Samsung Biomedical Research Institute (SBRI), Samsung Medical Center, Seoul 06351; BioMembrane Plasticity Research Center (MPRC), Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Myung-Soo
authors.initials: MS
authors.lastname: Kang
mesh_terms: D016923:Cell Death; D002460:Cell Line; D049109:Cell Proliferation; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism*; D018628:Gene Dosage; D055786:Gene Knockout Techniques; D018390:Gene Targeting; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D010957:Plasmids; D014162:Transfection
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens; C417029:EBV-encoded nuclear antigen 1