ArticleNature methods2019
Biological plasticity rescues target activity in CRISPR knock outs.
Article in Nature methods, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed.
- Frameshift Mutations in Exon 1 ofJournal of developmental biology · 2026Article
- LncRNA modulates Dpp-mediated wing development to influence flight in Aedes aegypti.Cellular and molecular life sciences : CMLS · 2026Article
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- Molecular characterization of Cdh12-SCON conditional knockout mice reveals unexpected splicing changes.Transgenic research · 2026Article
- All-in-one, Cas13d-based cell-specific gene knockdown system for zebrafish.bioRxiv : the preprint server for biology · 2026Article
- tRNA-based polycistronic CRISPR/Cas9 system boosts efficiency of multi-gene deletion in the moss Physcomitrella.Plant methods · 2026Article
- Loss-of-function mutations in the melanocortin-2-receptor (mc2r) lead to skin hyperpigmentation in teleost fish.Scientific reports · 2026Article
- Towards a cleaner CHO chassis: systematic knockout of host cell proteins for efficient biopharmaceutical manufacturing.Frontiers in bioengineering and biotechnology · 2026Article
- IRF1 mediates airway epithelial innate memory through priming BRD4- EP300 activity.Frontiers in immunology · 2026Article
- Turnover of missense mutant cytosolic proteins proceeds in the absence of major quality control E3 ligases.microPublication biology · 2026Article
- Review
- Translational Control in Cardiac Pathophysiology and Therapeutic Development: When mRNA Meets the Heart.International journal of molecular sciences · 2025Review
- Proteomic compensation by paralogs preserves protein interaction networks after gene loss in cancer.Molecular systems biology · 2025Article
- Knocking out ARL13B completely abolishes primary ciliogenesis in cell lines.Scientific reports · 2025Article
- DNA 5mC methylation inhibits the formation of G-quadruplex structures in the genome.Genome biology · 2025Article
- A global genetic interaction map of a human cell reveals conserved principles of genetic networks.bioRxiv : the preprint server for biology · 2025Article
- CRISPR GENome and epigenome engineering improves loss-of-function genetic-screening approaches.Cell reports methods · 2025Article
- Engineering novel CRISPRi repressors for highly efficient mammalian gene regulation.Genome biology · 2025Article
- VPAC1 and VPAC2 Receptor Heterozygosity Confers Distinct Biological Properties to BV2 Microglial Cells.Cells · 2025Article
- Plasmolipin deficiency is essential for HUVECs survival under hypoxic conditions.Cell death discovery · 2025Article
66 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene knock outs (KOs) are efficiently engineered through CRISPR-Cas9-induced frameshift mutations. While the efficiency of DNA editing is readily verified by DNA sequencing, a systematic understanding of the efficiency of protein elimination has been lacking. Here we devised an experimental strategy combining RNA sequencing and triple-stage mass spectrometry to characterize 193 genetically verified deletions targeting 136 distinct genes generated by CRISPR-induced frameshifts in HAP1 cells. We observed residual protein expression for about one third of the quantified targets, at variable levels from low to original, and identified two causal mechanisms, translation reinitiation leading to N-terminally truncated target proteins or skipping of the edited exon leading to protein isoforms with internal sequence deletions. Detailed analysis of three truncated targets, BRD4, DNMT1 and NGLY1, revealed partial preservation of protein function. Our results imply that systematic characterization of residual protein expression or function in CRISPR-Cas9-generated KO lines is necessary for phenotype interpretation.
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