Generating a viruse exclusively utilizing human epidermal growth factor as the entry receptor

Hongsheng Dai, Purdue University

Abstract

Cancer is the uncontrolled growth of abnormal cells resulting from the accumulation of genetic and epigenetic alterations. Over the past 3 decades, considerable knowledge of cancer biology has been accumulated, as a consequence, a plethora of novel targeted cancer therapies are being developed. An emerging treatment is oncolytic virotherapy, which uses therapeutic viruses to selectively infect and kill cancer cells while sparing normal tissues. An ideal oncolytic virus should preferentially or exclusively infect and replicate within cancer cells, and cause only mild or no human disease. However, the successful use of oncolytic virotherapy is impeded by the paucity of highly efficient cancer-specific oncolytic vectors. Sindbis virus has many advantages to be an excellent oncolytic viral vector. Attaching a specific targeting ligand to Sindbis virus particles might retarget Sindbis to a specific receptor. However, it has been shown that Sindbis virus has multiple receptor sites; such a strategy could not completely ablate native Sindbis receptors binding and yield a highly specific targeted vector. Furthermore, the structural constraints of the icosahedral symmetry of Sindbis viruses often make displaying specificity domains incompatible with efficient particle assembly. During my PhD training, I developed new methods for making Sindbis-based oncolytic vector with exclusive specificity to EGFR. Our strategy of developing targeted viral vector could be extended to other viral systems and target molecules.

Degree

Ph.D.

Advisors

Kuhn, Purdue University.

Subject Area

Molecular biology|Virology

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