Nature geneticsOct 14, 2025

Using activity to improve mutation scanning with base editors

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Activity-based co-selection made base editor mutational screens cleaner by enriching cells with high editing activity.

Evidence

A base-editing platform experiment developed the co-selection method and compared it with a traditional screen using tiled guide RNAs across TP53.

Caveat

The abstract demonstrates one target-locus benchmark and anticipates broader use, so general performance across other loci and applications remains untested here.

Simplified

Base editing is a CRISPR-based technology that enables high-throughput, nucleotide-level functional interrogation of the genome that is essential for understanding the genetic basis of human disease and informing therapeutic development. Base editing screens have emerged as a powerful experimental approach, yet significant cell-to-cell variability in editing efficiency introduces noise that may obscure meaningful results. Here we develop a co-selection method that enriches for cells with high base editing activity, substantially increasing editing efficiency at a target locus. We evaluate this activity-based selection method against a traditional screening approach by tiling guide RNAs across TP53, demonstrating its enhanced capacity to pinpoint specific mutations and protein regions of functional importance. We anticipate that this modular selection method will enhance the resolution of base editing screens across many applications.