CRISPRi multi-gene knockdowns show clear shell effects as perturbation biology converges on one idea
anshulkundaje · x · 2026-09-10
The Salis lab recounts that many-target CRISPRi experiments regularly produce clear first, second and third 'shells' of direct and indirect gene responses, with large secondary/tertiary fold-changes, as illustrated in their 2019 Nature Biotechnology paper.
- Their ELSA approach stably coexpresses 22 sgRNAs in nonrepetitive extra-long arrays, repressing up to 13 genes by up to 3,500-fold while avoiding genetic instability from repetitive DNA.
- The toolboxes of nonrepetitive parts were built with biophysical modeling, biochemical characterization and machine learning.
- The thread also highlights a converging idea in perturbation biology—how cells fluctuate before a perturbation predicts their response after it—which underpins the CIPHER method.
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