Why the study?
A rapid and straightforward approach to determining enteroviral receptors is necessary because the efficacy of oncolytic virotherapy depends on identifying the receptor used for cell entry and its presence on cancer cells.
The establishment of this knockout cell line panel provides a rapid approach to identifying enteroviral receptors, which is crucial for developing patient-specific oncolytic virotherapies.
Knockout cell panel speeds enteroviral receptor identification; leaves open translation to patient-specific oncolytic virotherapies.
Non-pathogenic natural and recombinant strains of human Enteroviruses are the subject of ongoing study with some strains having been approved for use as anticancer agents. The efficacy of oncolytic virotherapy depends upon identifying the receptor utilized by a specific strain for cell entry, and the presence of this receptor on the surface of cancer cells. Accordingly, a rapid and straightforward approach to determining the enteroviral receptors is necessary for developing an effective patient-specific, virus-based cancer therapy. To this end, we created a panel of seven lines with double knockouts on the background of the HEK293T cell line, which lacks the IFNAR1 gene. In these lines, the main viral receptor genes, including PVR, CXADR, CD55, ITGA2, SCARB2, ICAM1, and FCGRT, were knocked out using the CRISPR/Cas9 system. The panel of lines was validated on twelve different Enteroviruses types, providing a basis for studying the molecular mechanisms of enterovirus entry into cells, and for developing new therapeutic strains.
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Sosnovtseva et al. (2025) studied this question.
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