What question did this study set out to answer?

Identify host cellular genes and pathways that restrict or modulate the uptake, payload delivery, and efficiency of nonviral Cas-based nuclease and base editing tools in human cells.

August 15, 2026Nature CommunicationsOpen Access

Genome-wide CRISPR screening identifies cellular factors controlling nonviral genome editing efficiency

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Authors

SSShivani SaxenaUniversity of Wisconsin System MKMeha KabraUniversity of Wisconsin–Madison AAAmr A. AbdeenUniversity of Wisconsin–Madison

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Implication

In vitro genetic screen uncovers host genes restricting nonviral editing delivery in human cells, indicating targets to boost therapeutic editing efficiency.

Key Points

Identify host cellular genes and pathways that restrict or modulate the uptake, payload delivery, and efficiency of nonviral Cas-based nuclease and base editing tools in human cells.
Conducted a genome-wide CRISPR knockout screen targeting 19,114 genes across a pool of >200 million HEK293 cells.
Tracked library sgRNA identity and editing outcomes simultaneously on single amplicons using short-read sequencing to computationally isolate edited from unedited cells.
Validated candidate hits using arrayed knockouts with lipid-based nanoparticle Cas9 delivery in HEK293 cells and patient-derived human retinal pigment epithelium (RPE) cells derived from pluripotent stem cells.
Identified six host gene knockouts that increased nonviral genome editing efficiency by up to five-fold in human cells.
Arrayed knockouts of top candidates boosted lipid nanoparticle-mediated Cas9 editing efficiency from 5% to 50%.
Knockout of BET1L, GJB2, and MS4A13 increased targeted genome editing efficiency by over five-fold in patient-derived human RPE cells.

Cite This Study

Saxena et al. (2026) studied this question.

synapsesocial.com/papers/6a80194675c2e31742c85520 https://doi.org/10.1038/s41467-026-76350-5

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Implication

In vitro genetic screen uncovers host genes restricting nonviral editing delivery in human cells, indicating targets to boost therapeutic editing efficiency.

Genome-wide CRISPR screening identifies cellular factors controlling nonviral genome editing efficiency

Discussion

Member takes

Implication

Key Points

Cite This Study

Genome-wide CRISPR screening identifies cellular factors controlling nonviral genome editing efficiency

Discussion

Member takes

Implication

Key Points

Cite This Study

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