Bioengineering ZIKV-like Exosomes in the Treatment of Drug- Resistant Glioblastoma

SUMMARY Oncolytic viruses are becoming one of the most promising avenues of therapy against a diverse range of cancers due to inherent tumour specificity. Classically, the difficulty associated with the use of viruses for cancer treatment has been how to minimize off target effects. Currently, several modified viruses, mostly DNA viruses, have overcome this barrier and proceeded to phase III clinical trials with a version of the herpes simplex virus becoming the first oncolytic virus to gain FDA approval. With increased exploration of other viruses in the search for cancer therapeutics it was recently determined that the Zika virus possesses enhanced specificity towards the infection of glioblastoma stem cells (GSCs). As GSCs are responsible for the generation of prevalent, drug resistant, poor prognosis glioblastoma it has been hypothesized that the Zika virus could be utilized to effectively treat glioblastoma however, no further studies have been conducted as of yet. This paper proposes the mechanism behind enhanced Zika infection of GSCs along with a novel virus-like exosome system, the Zikasome, in which the specificity of the Zika virus for GSCs can be integrated with the ability of exosomes to transport therapeutics throughout the body to precisely combat glioblastoma. The goal of this paper is not only to better understand how the Zika virus can be employed to treat lethal glioblastoma but to build upon this proposed virus-like exosome system to develop a customisable virus-exosomal “cassette” that can be used in the treatment of any cancer in which virus specificity exists for. The development of such a system would have a revolutionary impact in the field of cancer treatment as many types of cancer that were previously untreatable could be targeted with a high degree of specificity while bypassing the problem of off target effects associated with the utilization of viruses themselves.