Isolation of Potential Oncolytic Mutants of Tanapoxvirus with Targeted Deletions and Insertions
Date of Award
Master of Science
Dr. Karim Essani
Dr. Bruce Bejcek
Dr. Brian Tripp
Tanapoxvirus, Oncolytic-TPV, TPV-2L, TPV-66R, FLiC
Masters Thesis-Abstract Only
Restricted to Campus until
Cancer remains a major health problem despite the advances in conventional cancer therapy. Remarkable advances in molecular biology and genetic engineering have improved the possibility of a novel cancer treatment using animal viruses, called oncolytic viruses. Patients receiving this kind of therapy may develop immunity against the viral therapy, thereby limiting the extended use of the same oncolytic virus multiple times. As such, a large pool of oncolytic viruses must be available for the success of such a therapy. Here, we describe several Tanapoxvirus (TPV) mutant viruses designed for this purpose. TPVK02LmCherry is a genetically modified TPV, which lacks the 2L protein that has been shown to bind and inhibit the biological activities of multiple human cytokines. TPVK02L/66R is a double knockout TPV, where 2L and 66R (viral thymidine kinase) genes are both deleted. These mutants may potentially enhance the viral tropism toward the cancer cells rather than normal cells. Further engineering of the TPV for the aim of activating the anti-tumor innate immunity was achieved by inserting the bacterial flagellin (FLiC) gene into the viral genome (TPVK066R/2L-FliC). This multi-mechanistic approach may enhance the oncolytic properties of TPV as an oncolytic virus.
Elswad, Mohamed Abdusalam, "Isolation of Potential Oncolytic Mutants of Tanapoxvirus with Targeted Deletions and Insertions" (2013). Masters Theses. 121.