<p>Directed evolution as a tool for the selection of oncolytic RNA viruses with desired phenotypes</p>

Abstract

Viruses have some characteristics in common with cell-based life. They can evolve and adapt to environmental conditions. Directed evolution can be used by researchers to produce viral strains with desirable phenotypes. Through bioselection, improved strains of oncolytic viruses can be obtained that have better safety profiles, increased specificity for malignant cells, and more efficient spread among tumor cells. It is also possible to select strains capable of killing a broader spectrum of cancer cell variants, so as to achieve a higher frequency of therapeutic responses. This review describes and analyses virus adaptation studies performed with members of four RNA virus families that are used for viral oncolysis: reoviruses, paramyxoviruses, enteroviruses, and rhabdoviruses.

The Challenges of Vaccine Development against Betacoronaviruses: Antibody Dependent Enhancement and Sendai Virus as a Possible Vaccine Vector

“…Moreover, SeV can be adapted to grow in FDA-approved mammalian cell lines. Multiple rounds of directed evolution increase the virus titer in various cell cultures [ 104 – 106 ].…”

Synthetic and systems biology principles in the design of programmable oncolytic virus immunotherapies for glioblastoma

“…The size of genetic circuits used to program OVs is fundamentally limited by the quantity of DNA that can be packaged, which ranges from 4 to 15 Kb depending on the viral vector chosen. 71 Recently developed modular DNA assembly techniques that take advantage of Golden Gate and Gibson assembly reactions have been shown to efficiently construct multigene expression vectors of reasonable construct size that can be packaged into a lentivirus and integrated into the genome. 72 Moreover, there are several design strategies that may be used to optimize genetic circuit size.…”

Experimental virus evolution in cancer cell monolayers, spheroids, and tissue explants

“…Experimental virus evolution has been used for investigating basic evolutionary processes under controlled laboratory conditions, as well as for clinical applications. These applications include the production of live attenuated vaccines ( Martín and Minor 2002 ), analysis of vaccine reversion to virulent phenotypes ( Stern et al 2017 ), modeling viral emergence in the laboratory ( Elena, Fraile, and García-Arenal 2014 ; Morley, Mendiola, and Turner 2015 ; Pepin et al 2019 ), predicting the appearance of drug resistances ( Dickinson et al 2014 ), and optimization of therapeutic viruses ( Sanjuán and Grdzelishvili 2015 ; Zainutdinov et al 2019 ). For experimental virus evolution to provide useful results, though, laboratory conditions should reproduce relevant selective pressures found in nature ( Geoghegan and Holmes 2018 : 40).…”

“…This limitation is further accentuated by the fact that tumor cells are a highly heterogeneous, evolving target ( McGranahan and Swanton 2017 ), complicating the design of therapeutic viruses for each specific cell type. Directed evolution offers an alternative approach, in which selection can be harnessed to adapt viruses to specific target cells even if the underlying mechanisms are not initially understood ( Sanjuán and Grdzelishvili 2015 ; Zainutdinov et al 2019 ). Yet, the number of directed evolution studies with oncolytic viruses is relatively small and, surprisingly, most of these studies have been performed with DNA viruses, particularly adenoviruses ( Yan et al 2003 ; Subramanian, Vijayalingam, and Chinnadurai 2006 ; Gros et al 2008 ; Kuhn et al 2008 ; Puig-Saus et al 2012 ; Wechman et al 2016 ), despite the fact that RNA viruses exhibit higher mutation rates ( Sanjuán and Domingo-Calap 2016 ) and, hence, should lend themselves more easily to evolutionary optimization.…”