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bioRxiv · 10.64898/2026.03.06.710083

Elucidating genes sufficient for viral entry into cells through sequential genome-wide CRISPR activation screens

Chai, T.·Wong, A.·Yin, Q.·von Creytz, I.·Weissman, J. S.·Saunders, R. A.·Prescott, J. B.·Loh, K. M.
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Abstract

A preeminent goal of virology is to discover cellular genes that mediate virus entry. Genome-wide loss-of-function screens can illuminate single genes necessary for virus entry, but are stymied by genetic redundancy. Here we report a genome-wide CRISPR activation screening strategy to discover single genes that are sufficient for viral entry into normally-uninfectable cells. Sequential rounds of viral infection vastly enhanced screening sensitivity. This sequential screening strategy was generalizable to two unrelated viruses--Ebola and rabies viruses--and could broadly accelerate the discovery of viral entry factors.

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Chai, T., Wong, A., Yin, Q., von Creytz, I., Weissman, J. S., Saunders, R. A., Prescott, J. B., Loh, K. M.. 2026-03-06. Elucidating genes sufficient for viral entry into cells through sequential genome-wide CRISPR activation screens. https://doi.org/10.64898/2026.03.06.710083

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