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Directed Evolution as a Tool for the Selection of Oncolytic RNA Viruses With Desired Phenotypes


Directed Evolution as a Tool for the Selection of Oncolytic RNA Viruses With Desired Phenotypes

Sergei S Zainutdinov et al. Oncolytic Virother.


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.

Keywords: directed viral evolution; oncolytic viruses; virus adaptation; virus selection.

Conflict of interest statement

Mr. Sergei S Zainutdinov reports grants from the Russian Foundation for Basic Research, during the conduct of the study. The authors report no other conflicts of interest in this work.


Figure 1
Figure 1
Selection process for broadening virus infectivity. Steps 5 or/and 6 might be omitted in some experiments.
Figure 2
Figure 2
Selection process for increasing Newcastle Disease Virus (NDV) intratumoral spreading ability.
Figure 3
Figure 3
Changes in Sendai virus phenotype and genotype during adaptation to cell culture. SeV strains adapted to grow in 4,647 or HEK293-cell cultures lost their oncolytic properties. They were subjected to reverse passaging in embryonated chicken eggs for evaluation of their ability to restore their oncolytic potentials.
Figure 4
Figure 4
Testing phenotype and genotype stabilities of attenuated poliovirus recombinant.

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