ArticleNature biotechnology2020
Titrating gene expression using libraries of systematically attenuated CRISPR guide RNAs.
Article in Nature biotechnology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed, 170 citations in OpenAlex.
- Utilization of the CRISPR-Cas system for investigating tuberculosis drug resistance.Molecular biology reports · 2026Review
- Optimized parameters for CRISPR-Cas9 interference library design.Cell genomics · 2026Article
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- Chemical and Structural Engineering of Guide RNAs for Precision Genome Editing: From Design Principles to Clinical Applications.Chemical biology & drug design · 2026Review
- Orthogonal CRISPR screens and human liver chimeric mice identify hepatitis B virus host factors.bioRxiv : the preprint server for biology · 2026Article
- Programmable CRISPRtune dissects the transcriptional repressive activity of MeCP2.bioRxiv : the preprint server for biology · 2026Article
- Buffering of gene dosage response curves for human complex traits.Cell genomics · 2026Article
- Mesoscopic Calculation of Single Mismatches in RNA/DNA Hybrids: Strong Hydrogen Bonds of dTrG Affect CRISPR Off-Target Binding.The journal of physical chemistry. B · 2026Article
- High-throughput evaluation of in vitro CRISPR activities enables optimized large-scale multiplex enrichment of rare variants.Nature biomedical engineering · 2026Article
- Perturbation of genes linked to common schizophrenia risk variants identifies cilia programs.bioRxiv : the preprint server for biology · 2026Article
- Dose as a fundamental organizing principle in physiology: Implications for mechanism, disease, and precision medicine.Journal of precision medicine (Amsterdam, Netherlands) · 2026Article
- Systematic mapping of chromatin dysregulation driven by viral transcriptional regulators at scale.bioRxiv : the preprint server for biology · 2026Article
- DNA hypomethylation-activated PRAME drives early-stage lung adenocarcinoma recurrence via ZNF740 and PI3K/AKT/mTOR signaling.Translational lung cancer research · 2026Article
- Article
- Genome-wide single-cell perturbation screens with VIPerturb-seq.bioRxiv : the preprint server for biology · 2026Article
- Mismatch tolerance of a gRNA for CRISPR-based gene activation confers broad activity critical for cell reprogramming.bioRxiv : the preprint server for biology · 2026Article
- Nonlinear transcriptional responses to gradual modulation of transcription factor dosage.eLife · 2026Article
- The Emergence of a CRISPR-Cas Revolution in Ecology: Applications, Challenges, and an Ecologist's Overview of the Toolbox.Molecular ecology resources · 2026Review
- GeneSNAKE: a Python package for simulation of gene regulatory networks and perturbation-induced expression data.Bioinformatics advances · 2026Article
- A parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording.Nature biotechnology · 2025Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
A lack of tools to precisely control gene expression has limited our ability to evaluate relationships between expression levels and phenotypes. Here, we describe an approach to titrate expression of human genes using CRISPR interference and series of single-guide RNAs (sgRNAs) with systematically modulated activities. We used large-scale measurements across multiple cell models to characterize activities of sgRNAs containing mismatches to their target sites and derived rules governing mismatched sgRNA activity using deep learning. These rules enabled us to synthesize a compact sgRNA library to titrate expression of ~2,400 genes essential for robust cell growth and to construct an in silico sgRNA library spanning the human genome. Staging cells along a continuum of gene expression levels combined with single-cell RNA-seq readout revealed sharp transitions in cellular behaviors at gene-specific expression thresholds. Our work provides a general tool to control gene expression, with applications ranging from tuning biochemical pathways to identifying suppressors for diseases of dysregulated gene expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.